TY - JOUR
AB - We consider the problem of computing the set of initial states of a dynamical system such that there exists a control strategy to ensure that the trajectories satisfy a temporal logic specification with probability 1 (almost-surely). We focus on discrete-time, stochastic linear dynamics and specifications given as formulas of the Generalized Reactivity(1) fragment of Linear Temporal Logic over linear predicates in the states of the system. We propose a solution based on iterative abstraction-refinement, and turn-based 2-player probabilistic games. While the theoretical guarantee of our algorithm after any finite number of iterations is only a partial solution, we show that if our algorithm terminates, then the result is the set of all satisfying initial states. Moreover, for any (partial) solution our algorithm synthesizes witness control strategies to ensure almost-sure satisfaction of the temporal logic specification. While the proposed algorithm guarantees progress and soundness in every iteration, it is computationally demanding. We offer an alternative, more efficient solution for the reachability properties that decomposes the problem into a series of smaller problems of the same type. All algorithms are demonstrated on an illustrative case study.
AU - Svoreňová, Mária
AU - Kretinsky, Jan
AU - Chmelik, Martin
AU - Chatterjee, Krishnendu
AU - Cěrná, Ivana
AU - Belta, Cǎlin
ID - 1407
IS - 2
JF - Nonlinear Analysis: Hybrid Systems
TI - Temporal logic control for stochastic linear systems using abstraction refinement of probabilistic games
VL - 23
ER -
TY - CONF
AB - We study probabilistic models of natural images and extend the autoregressive family of PixelCNN models by incorporating latent variables. Subsequently, we describe two new generative image models that exploit different image transformations as latent variables: a quantized grayscale view of the image or a multi-resolution image pyramid. The proposed models tackle two known shortcomings of existing PixelCNN models: 1) their tendency to focus on low-level image details, while largely ignoring high-level image information, such as object shapes, and 2) their computationally costly procedure for image sampling. We experimentally demonstrate benefits of our LatentPixelCNN models, in particular showing that they produce much more realistically looking image samples than previous state-of-the-art probabilistic models.
AU - Kolesnikov, Alexander
AU - Lampert, Christoph
ID - 1000
SN - 978-151085514-4
T2 - 34th International Conference on Machine Learning
TI - PixelCNN models with auxiliary variables for natural image modeling
VL - 70
ER -
TY - CONF
AB - We present a computational approach for designing CurveUps, curvy shells that form from an initially flat state. They consist of small rigid tiles that are tightly held together by two pre-stretched elastic sheets attached to them. Our method allows the realization of smooth, doubly curved surfaces that can be fabricated as a flat piece. Once released, the restoring forces of the pre-stretched sheets support the object to take shape in 3D. CurveUps are structurally stable in their target configuration. The design process starts with a target surface. Our method generates a tile layout in 2D and optimizes the distribution, shape, and attachment areas of the tiles to obtain a configuration that is fabricable and in which the curved up state closely matches the target. Our approach is based on an efficient approximate model and a local optimization strategy for an otherwise intractable nonlinear optimization problem. We demonstrate the effectiveness of our approach for a wide range of shapes, all realized as physical prototypes.
AU - Guseinov, Ruslan
AU - Miguel, Eder
AU - Bickel, Bernd
ID - 1001
IS - 4
TI - CurveUps: Shaping objects from flat plates with tension-actuated curvature
VL - 36
ER -
TY - CONF
AB - We present an interactive design system to create functional mechanical objects. Our computational approach allows novice users to retarget an existing mechanical template to a user-specified input shape. Our proposed representation for a mechanical template encodes a parameterized mechanism, mechanical constraints that ensure a physically valid configuration, spatial relationships of mechanical parts to the user-provided shape, and functional constraints that specify an intended functionality. We provide an intuitive interface and optimization-in-the-loop approach for finding a valid configuration of the mechanism and the shape to ensure that higher-level functional goals are met. Our algorithm interactively optimizes the mechanism while the user manipulates the placement of mechanical components and the shape. Our system allows users to efficiently explore various design choices and to synthesize customized mechanical objects that can be fabricated with rapid prototyping technologies. We demonstrate the efficacy of our approach by retargeting various mechanical templates to different shapes and fabricating the resulting functional mechanical objects.
AU - Zhang, Ran
AU - Auzinger, Thomas
AU - Ceylan, Duygu
AU - Li, Wilmot
AU - Bickel, Bernd
ID - 1002
IS - 4
SN - 07300301
TI - Functionality-aware retargeting of mechanisms to 3D shapes
VL - 36
ER -
TY - CONF
AB - Network games (NGs) are played on directed graphs and are extensively used in network design and analysis. Search problems for NGs include finding special strategy profiles such as a Nash equilibrium and a globally optimal solution. The networks modeled by NGs may be huge. In formal verification, abstraction has proven to be an extremely effective technique for reasoning about systems with big and even infinite state spaces. We describe an abstraction-refinement methodology for reasoning about NGs. Our methodology is based on an abstraction function that maps the state space of an NG to a much smaller state space. We search for a global optimum and a Nash equilibrium by reasoning on an under- and an overapproximation defined on top of this smaller state space. When the approximations are too coarse to find such profiles, we refine the abstraction function. Our experimental results demonstrate the efficiency of the methodology.
AU - Avni, Guy
AU - Guha, Shibashis
AU - Kupferman, Orna
ID - 1003
SN - 10450823
TI - An abstraction-refinement methodology for reasoning about network games
ER -
TY - JOUR
AB - The fundamental tasks of the root system are, besides anchoring, mediating interactions between plant and soil and providing the plant with water and nutrients. The architecture of the root system is controlled by endogenous mechanisms that constantly integrate environmental signals, such as availability of nutrients and water. Extremely important for efficient soil exploitation and survival under less favorable conditions is the developmental flexibility of the root system that is largely determined by its postembryonic branching capacity. Modulation of initiation and outgrowth of lateral roots provides roots with an exceptional plasticity, allows optimal adjustment to underground heterogeneity, and enables effective soil exploitation and use of resources. Here we discuss recent advances in understanding the molecular mechanisms that shape the plant root system and integrate external cues to adapt to the changing environment.
AU - Ötvös, Krisztina
AU - Benková, Eva
ID - 1004
JF - Current Opinion in Genetics & Development
SN - 0959437X
TI - Spatiotemporal mechanisms of root branching
VL - 45
ER -
TY - JOUR
AB - A nonlinear system possesses an invariance with respect to a set of transformations if its output dynamics remain invariant when transforming the input, and adjusting the initial condition accordingly. Most research has focused on invariances with respect to time-independent pointwise transformations like translational-invariance (u(t) -> u(t) + p, p in R) or scale-invariance (u(t) -> pu(t), p in R>0). In this article, we introduce the concept of s0-invariances with respect to continuous input transformations exponentially growing/decaying over time. We show that s0-invariant systems not only encompass linear time-invariant (LTI) systems with transfer functions having an irreducible zero at s0 in R, but also that the input/output relationship of nonlinear s0-invariant systems possesses properties well known from their linear counterparts. Furthermore, we extend the concept of s0-invariances to second- and higher-order s0-invariances, corresponding to invariances with respect to transformations of the time-derivatives of the input, and encompassing LTI systems with zeros of multiplicity two or higher. Finally, we show that nth-order 0-invariant systems realize – under mild conditions – nth-order nonlinear differential operators: when excited by an input of a characteristic functional form, the system’s output converges to a constant value only depending on the nth (nonlinear) derivative of the input.
AU - Lang, Moritz
AU - Sontag, Eduardo
ID - 1007
JF - Automatica
SN - 00051098
TI - Zeros of nonlinear systems with input invariances
VL - 81C
ER -
TY - CONF
AB - A standard objective in partially-observable Markov decision processes (POMDPs) is to find a policy that maximizes the expected discounted-sum payoff. However, such policies may still permit unlikely but highly undesirable outcomes, which is problematic especially in safety-critical applications. Recently, there has been a surge of interest in POMDPs where the goal is to maximize the probability to ensure that the payoff is at least a given threshold, but these approaches do not consider any optimization beyond satisfying this threshold constraint. In this work we go beyond both the “expectation” and “threshold” approaches and consider a “guaranteed payoff optimization (GPO)” problem for POMDPs, where we are given a threshold t and the objective is to find a policy σ such that a) each possible outcome of σ yields a discounted-sum payoff of at least t, and b) the expected discounted-sum payoff of σ is optimal (or near-optimal) among all policies satisfying a). We present a practical approach to tackle the GPO problem and evaluate it on standard POMDP benchmarks.
AU - Chatterjee, Krishnendu
AU - Novotny, Petr
AU - Pérez, Guillermo
AU - Raskin, Jean
AU - Zikelic, Djordje
ID - 1009
T2 - Proceedings of the 31st AAAI Conference on Artificial Intelligence
TI - Optimizing expectation with guarantees in POMDPs
VL - 5
ER -
TY - JOUR
AB - We prove a local law in the bulk of the spectrum for random Gram matrices XX∗, a generalization of sample covariance matrices, where X is a large matrix with independent, centered entries with arbitrary variances. The limiting eigenvalue density that generalizes the Marchenko-Pastur law is determined by solving a system of nonlinear equations. Our entrywise and averaged local laws are on the optimal scale with the optimal error bounds. They hold both in the square case (hard edge) and in the properly rectangular case (soft edge). In the latter case we also establish a macroscopic gap away from zero in the spectrum of XX∗.
AU - Alt, Johannes
AU - Erdös, László
AU - Krüger, Torben H
ID - 1010
JF - Electronic Journal of Probability
SN - 10836489
TI - Local law for random Gram matrices
VL - 22
ER -
TY - CONF
AB - Pushdown systems (PDSs) and recursive state machines (RSMs), which are linearly equivalent, are standard models for interprocedural analysis. Yet RSMs are more convenient as they (a) explicitly model function calls and returns, and (b) specify many natural parameters for algorithmic analysis, e.g., the number of entries and exits. We consider a general framework where RSM transitions are labeled from a semiring and path properties are algebraic with semiring operations, which can model, e.g., interprocedural reachability and dataflow analysis problems. Our main contributions are new algorithms for several fundamental problems. As compared to a direct translation of RSMs to PDSs and the best-known existing bounds of PDSs, our analysis algorithm improves the complexity for finite-height semirings (that subsumes reachability and standard dataflow properties). We further consider the problem of extracting distance values from the representation structures computed by our algorithm, and give efficient algorithms that distinguish the complexity of a one-time preprocessing from the complexity of each individual query. Another advantage of our algorithm is that our improvements carry over to the concurrent setting, where we improve the bestknown complexity for the context-bounded analysis of concurrent RSMs. Finally, we provide a prototype implementation that gives a significant speed-up on several benchmarks from the SLAM/SDV project.
AU - Chatterjee, Krishnendu
AU - Kragl, Bernhard
AU - Mishra, Samarth
AU - Pavlogiannis, Andreas
ED - Yang, Hongseok
ID - 1011
SN - 03029743
TI - Faster algorithms for weighted recursive state machines
VL - 10201
ER -
TY - JOUR
AB - Vortices are commonly observed in the context of classical hydrodynamics: from whirlpools after stirring the coffee in a cup to a violent atmospheric phenomenon such as a tornado, all classical vortices are characterized by an arbitrary circulation value of the local velocity field. On the other hand the appearance of vortices with quantized circulation represents one of the fundamental signatures of macroscopic quantum phenomena. In two-dimensional superfluids quantized vortices play a key role in determining finite-temperature properties, as the superfluid phase and the normal state are separated by a vortex unbinding transition, the Berezinskii-Kosterlitz-Thouless transition. Very recent experiments with two-dimensional superfluid fermions motivate the present work: we present theoretical results based on the renormalization group showing that the universal jump of the superfluid density and the critical temperature crucially depend on the interaction strength, providing a strong benchmark for forthcoming investigations.
AU - Bighin, Giacomo
AU - Salasnich, Luca
ID - 1015
JF - Scientific Reports
SN - 20452322
TI - Vortices and antivortices in two-dimensional ultracold Fermi gases
VL - 7
ER -
TY - JOUR
AB - The integrity and dynamic properties of the microtubule cytoskeleton are indispensable for the development of the mammalian brain. Consequently, mutations in the genes that encode the structural component (the α/β-tubulin heterodimer) can give rise to severe, sporadic neurodevelopmental disorders. These are commonly referred to as the tubulinopathies. Here we report the addition of recessive quadrupedalism, also known as Uner Tan syndrome (UTS), to the growing list of diseases caused by tubulin variants. Analysis of a consanguineous UTS family identified a biallelic TUBB2B mutation, resulting in a p.R390Q amino acid substitution. In addition to the identifying quadrupedal locomotion, all three patients showed severe cerebellar hypoplasia. None, however, displayed the basal ganglia malformations typically associated with TUBB2B mutations. Functional analysis of the R390Q substitution revealed that it did not affect the ability of β-tubulin to fold or become assembled into the α/β-heterodimer, nor did it influence the incorporation of mutant-containing heterodimers into microtubule polymers. The 390Q mutation in S. cerevisiae TUB2 did not affect growth under basal conditions, but did result in increased sensitivity to microtubule-depolymerizing drugs, indicative of a mild impact of this mutation on microtubule function. The TUBB2B mutation described here represents an unusual recessive mode of inheritance for missense-mediated tubulinopathies and reinforces the sensitivity of the developing cerebellum to microtubule defects.
AU - Breuss, Martin
AU - Nguyen, Thai
AU - Srivatsan, Anjana
AU - Leca, Ines
AU - Tian, Guoling
AU - Fritz, Tanja
AU - Hansen, Andi H
AU - Musaev, Damir
AU - Mcevoy Venneri, Jennifer
AU - Kiely, James
AU - Rosti, Rasim
AU - Scott, Eric
AU - Tan, Uner
AU - Kolodner, Richard
AU - Cowan, Nicholas
AU - Keays, David
AU - Gleeson, Joseph
ID - 1016
IS - 2
JF - Human Molecular Genetics
SN - 09646906
TI - Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting microtubule stability
VL - 26
ER -
TY - JOUR
AB - The development of the vertebrate central nervous system is reliant on a complex cascade of biological processes that include mitotic division, relocation of migrating neurons, and the extension of dendritic and axonal processes. Each of these cellular events requires the diverse functional repertoire of the microtubule cytoskeleton for the generation of forces, assembly of macromolecular complexes and transport of molecules and organelles. The tubulins are a multi-gene family that encode for the constituents of microtubules, and have been implicated in a spectrum of neurological disorders. Evidence is building that different tubulins tune the functional properties of the microtubule cytoskeleton dependent on the cell type, developmental profile and subcellular localisation. Here we review of the origins of the functional specification of the tubulin gene family in the developing brain at a transcriptional, translational, and post-transcriptional level. We remind the reader that tubulins are not just loading controls for your average Western blot.
AU - Breuss, Martin
AU - Leca, Ines
AU - Gstrein, Thomas
AU - Hansen, Andi H
AU - Keays, David
ID - 1017
JF - Molecular and Cellular Neuroscience
SN - 10447431
TI - Tubulins and brain development: The origins of functional specification
VL - 84
ER -
TY - JOUR
AB - In plants, the multistep phosphorelay (MSP) pathway mediates a range of regulatory processes, including those activated by cytokinins. The crosstalk between cytokinin response and light is known for a long time. However, the molecular mechanism underlying the interactionbetween light and cytokinin signaling remains elusive. In the screen for upstream regulators we identified a LONG PALE HYPOCOTYL (LPH) gene whose activity is indispensable for spatiotemporally correct expression of CYTOKININ INDEPENDENT-1 (CKI1), encoding the constitutively active sensor histidine kinase that activates MSP signaling. lph is a new allele of HEME OXYGENASE 1 (HY1) which encodes the key protein in the biosynthesis of phytochromobilin, a cofactor of photoconvertiblephytochromes. Our analysis confirmed the light-dependent regulation oftheCKI1 expression pattern. We show that CKI1 expression is under the control of phytochrome A (phyA), functioning as a dual (both positive and negative) regulator of CKI1 expression, presumably via the phyA-regulated transcription factors PHYTOCHROME INTERACTING FACTOR 3 (PIF3) and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1). Changes in CKI1 expression observed in lph/hy1-7 and phy mutants correlatewithmisregulation of MSP signaling, changedcytokinin sensitivity and developmental aberrations,previously shown to be associated with cytokinin and/or CKI1 action. Besides that, we demonstrate novel role of phyA-dependent CKI1 expression in the hypocotyl elongation and hook development during skotomorphogenesis. Based on these results, we propose that the light-dependent regulation of CKI1 provides a plausible mechanistic link underlying the well-known interaction between light- and cytokinin-controlled plant development.
AU - Dobisova, Tereza
AU - Hrdinova, Vendula
AU - Cuesta, Candela
AU - Michlickova, Sarka
AU - Urbankova, Ivana
AU - Hejatkova, Romana
AU - Zadnikova, Petra
AU - Pernisová, Markéta
AU - Benková, Eva
AU - Hejátko, Jan
ID - 1018
IS - 1
JF - Plant Physiology
TI - Light regulated expression of sensor histidine kinase CKI1 controls cytokinin related development
VL - 174
ER -
TY - JOUR
AB - Cellulose is the most abundant biopolymer on Earth. Cellulose fibers, such as the one extracted form cotton or woodpulp, have been used by humankind for hundreds of years to make textiles and paper. Here we show how, by engineering light-matter interaction, we can optimize light scattering using exclusively cellulose nanocrystals. The produced material is sustainable, biocompatible, and when compared to ordinary microfiber-based paper, it shows enhanced scattering strength (×4), yielding a transport mean free path as low as 3.5 μm in the visible light range. The experimental results are in a good agreement with the theoretical predictions obtained with a diffusive model for light propagation.
AU - Caixeiro, Soraya
AU - Peruzzo, Matilda
AU - Onelli, Olimpia
AU - Vignolini, Silvia
AU - Sapienza, Riccardo
ID - 1020
IS - 9
JF - ACS Applied Materials and Interfaces
SN - 19448244
TI - Disordered cellulose based nanostructures for enhanced light scattering
VL - 9
ER -
TY - JOUR
AB - Most flows in nature and engineering are turbulent because of their large velocities and spatial scales. Laboratory experiments on rotating quasi-Keplerian flows, for which the angular velocity decreases radially but the angular momentum increases, are however laminar at Reynolds numbers exceeding one million. This is in apparent contradiction to direct numerical simulations showing that in these experiments turbulence transition is triggered by the axial boundaries. We here show numerically that as the Reynolds number increases, turbulence becomes progressively confined to the boundary layers and the flow in the bulk fully relaminarizes. Our findings support that turbulence is unlikely to occur in isothermal constant-density quasi-Keplerian flows.
AU - Lopez Alonso, Jose M
AU - Avila, Marc
ID - 1021
JF - Journal of Fluid Mechanics
SN - 00221120
TI - Boundary layer turbulence in experiments on quasi Keplerian flows
VL - 817
ER -
TY - JOUR
AB - We introduce a multiscale topological description of the Megaparsec web-like cosmic matter distribution. Betti numbers and topological persistence offer a powerful means of describing the rich connectivity structure of the cosmic web and of its multiscale arrangement of matter and galaxies. Emanating from algebraic topology and Morse theory, Betti numbers and persistence diagrams represent an extension and deepening of the cosmologically familiar topological genus measure and the related geometric Minkowski functionals. In addition to a description of the mathematical background, this study presents the computational procedure for computing Betti numbers and persistence diagrams for density field filtrations. The field may be computed starting from a discrete spatial distribution of galaxies or simulation particles. The main emphasis of this study concerns an extensive and systematic exploration of the imprint of different web-like morphologies and different levels of multiscale clustering in the corresponding computed Betti numbers and persistence diagrams. To this end, we use Voronoi clustering models as templates for a rich variety of web-like configurations and the fractal-like Soneira-Peebles models exemplify a range of multiscale configurations. We have identified the clear imprint of cluster nodes, filaments, walls, and voids in persistence diagrams, along with that of the nested hierarchy of structures in multiscale point distributions. We conclude by outlining the potential of persistent topology for understanding the connectivity structure of the cosmic web, in large simulations of cosmic structure formation and in the challenging context of the observed galaxy distribution in large galaxy surveys.
AU - Pranav, Pratyush
AU - Edelsbrunner, Herbert
AU - Van De Weygaert, Rien
AU - Vegter, Gert
AU - Kerber, Michael
AU - Jones, Bernard
AU - Wintraecken, Mathijs
ID - 1022
IS - 4
JF - Monthly Notices of the Royal Astronomical Society
SN - 00358711
TI - The topology of the cosmic web in terms of persistent Betti numbers
VL - 465
ER -
TY - JOUR
AB - We consider products of independent square non-Hermitian random matrices. More precisely, let X1,…, Xn be independent N × N random matrices with independent entries (real or complex with independent real and imaginary parts) with zero mean and variance 1/N. Soshnikov-O’Rourke [19] and Götze-Tikhomirov [15] showed that the empirical spectral distribution of the product of n random matrices with iid entries converges to (equation found). We prove that if the entries of the matrices X1,…, Xn are independent (but not necessarily identically distributed) and satisfy uniform subexponential decay condition, then in the bulk the convergence of the ESD of X1,…, Xn to (0.1) holds up to the scale N–1/2+ε.
AU - Nemish, Yuriy
ID - 1023
JF - Electronic Journal of Probability
SN - 10836489
TI - Local law for the product of independent non-Hermitian random matrices with independent entries
VL - 22
ER -
TY - JOUR
AB - Many organ surfaces are covered by a protective epithelial-cell layer. It emerges that such layers are maintained by cell stretching that triggers cell division mediated by the force-sensitive ion-channel protein Piezo1. See Letter p.118
AU - Heisenberg, Carl-Philipp J
ID - 1025
IS - 7643
JF - Nature
SN - 00280836
TI - Cell biology: Stretched divisions
VL - 543
ER -
TY - JOUR
AB - Auf der Suche nach einem Bibliothekssystem entschied sich die Forschungseinrichtung IST Austria im Jahr 2014 für das Open-Source-Produkt Koha. In einem ersten Schritt wurden zunächst Grundfunktionen aktiviert um im Anschluss diverse zusätzliche Tools zum Einsatz zu bringen. Die große Flexibilität des Systems erlaubt maßgeschneiderte Lösungen für unterschiedlichste Institutionen. Trotz Herausforderungen kann die Bibliothek auf eine erfolgreiche Implementierung zurückblicken.
AU - Villányi, Márton
ID - 1030
IS - 1
JF - Informationspraxis
SN - 2297-3249
TI - Ein freies Bibliothekssystem für wissenschaftliche Bibliotheken – Werkstattbericht der IST Austria Library
VL - 3
ER -
TY - JOUR
AB - A fundamental algorithmic problem at the heart of static analysis is Dyck reachability. The input is a graph where the edges are labeled with different types of opening and closing parentheses, and the reachability information is computed via paths whose parentheses are properly matched. We present new results for Dyck reachability problems with applications to alias analysis and data-dependence analysis. Our main contributions, that include improved upper bounds as well as lower bounds that establish optimality guarantees, are as follows: First, we consider Dyck reachability on bidirected graphs, which is the standard way of performing field-sensitive points-to analysis. Given a bidirected graph with n nodes and m edges, we present: (i) an algorithm with worst-case running time O(m + n · α(n)), where α(n) is the inverse Ackermann function, improving the previously known O(n2) time bound; (ii) a matching lower bound that shows that our algorithm is optimal wrt to worst-case complexity; and (iii) an optimal average-case upper bound of O(m) time, improving the previously known O(m · logn) bound. Second, we consider the problem of context-sensitive data-dependence analysis, where the task is to obtain analysis summaries of library code in the presence of callbacks. Our algorithm preprocesses libraries in almost linear time, after which the contribution of the library in the complexity of the client analysis is only linear, and only wrt the number of call sites. Third, we prove that combinatorial algorithms for Dyck reachability on general graphs with truly sub-cubic bounds cannot be obtained without obtaining sub-cubic combinatorial algorithms for Boolean Matrix Multiplication, which is a long-standing open problem. Thus we establish that the existing combinatorial algorithms for Dyck reachability are (conditionally) optimal for general graphs. We also show that the same hardness holds for graphs of constant treewidth. Finally, we provide a prototype implementation of our algorithms for both alias analysis and data-dependence analysis. Our experimental evaluation demonstrates that the new algorithms significantly outperform all existing methods on the two problems, over real-world benchmarks.
AU - Chatterjee, Krishnendu
AU - Choudhary, Bhavya
AU - Pavlogiannis, Andreas
ID - 10416
IS - POPL
JF - Proceedings of the ACM on Programming Languages
TI - Optimal Dyck reachability for data-dependence and Alias analysis
VL - 2
ER -
TY - JOUR
AB - We present a new dynamic partial-order reduction method for stateless model checking of concurrent programs. A common approach for exploring program behaviors relies on enumerating the traces of the program, without storing the visited states (aka stateless exploration). As the number of distinct traces grows exponentially, dynamic partial-order reduction (DPOR) techniques have been successfully used to partition the space of traces into equivalence classes (Mazurkiewicz partitioning), with the goal of exploring only few representative traces from each class.
We introduce a new equivalence on traces under sequential consistency semantics, which we call the observation equivalence. Two traces are observationally equivalent if every read event observes the same write event in both traces. While the traditional Mazurkiewicz equivalence is control-centric, our new definition is data-centric. We show that our observation equivalence is coarser than the Mazurkiewicz equivalence, and in many cases even exponentially coarser. We devise a DPOR exploration of the trace space, called data-centric DPOR, based on the observation equivalence.
AU - Chalupa, Marek
AU - Chatterjee, Krishnendu
AU - Pavlogiannis, Andreas
AU - Sinha, Nishant
AU - Vaidya, Kapil
ID - 10417
IS - POPL
JF - Proceedings of the ACM on Programming Languages
TI - Data-centric dynamic partial order reduction
VL - 2
ER -
TY - JOUR
AB - We present a new proof rule for proving almost-sure termination of probabilistic programs, including those that contain demonic non-determinism. An important question for a probabilistic program is whether the probability mass of all its diverging runs is zero, that is that it terminates "almost surely". Proving that can be hard, and this paper presents a new method for doing so. It applies directly to the program's source code, even if the program contains demonic choice. Like others, we use variant functions (a.k.a. "super-martingales") that are real-valued and decrease randomly on each loop iteration; but our key innovation is that the amount as well as the probability of the decrease are parametric. We prove the soundness of the new rule, indicate where its applicability goes beyond existing rules, and explain its connection to classical results on denumerable (non-demonic) Markov chains.
AU - Mciver, Annabelle
AU - Morgan, Carroll
AU - Kaminski, Benjamin Lucien
AU - Katoen, Joost P
ID - 10418
IS - POPL
JF - Proceedings of the ACM on Programming Languages
TI - A new proof rule for almost-sure termination
VL - 2
ER -
TY - JOUR
AB - The Ising model is one of the simplest and most famous models of interacting systems. It was originally proposed to model ferromagnetic interactions in statistical physics and is now widely used to model spatial processes in many areas such as ecology, sociology, and genetics, usually without testing its goodness-of-fit. Here, we propose an exact goodness-of-fit test for the finite-lattice Ising model. The theory of Markov bases has been developed in algebraic statistics for exact goodness-of-fit testing using a Monte Carlo approach. However, this beautiful theory has fallen short of its promise for applications, because finding a Markov basis is usually computationally intractable. We develop a Monte Carlo method for exact goodness-of-fit testing for the Ising model which avoids computing a Markov basis and also leads to a better connectivity of the Markov chain and hence to a faster convergence. We show how this method can be applied to analyze the spatial organization of receptors on the cell membrane.
AU - Martin Del Campo Sanchez, Abraham
AU - Cepeda Humerez, Sarah A
AU - Uhler, Caroline
ID - 2016
IS - 2
JF - Scandinavian Journal of Statistics
SN - 03036898
TI - Exact goodness-of-fit testing for the Ising model
VL - 44
ER -
TY - CONF
AB - We consider the problem of estimating the partition function Z(β)=∑xexp(−β(H(x)) of a Gibbs distribution with a Hamilton H(⋅), or more precisely the logarithm of the ratio q=lnZ(0)/Z(β). It has been recently shown how to approximate q with high probability assuming the existence of an oracle that produces samples from the Gibbs distribution for a given parameter value in [0,β]. The current best known approach due to Huber [9] uses O(qlnn⋅[lnq+lnlnn+ε−2]) oracle calls on average where ε is the desired accuracy of approximation and H(⋅) is assumed to lie in {0}∪[1,n]. We improve the complexity to O(qlnn⋅ε−2) oracle calls. We also show that the same complexity can be achieved if exact oracles are replaced with approximate sampling oracles that are within O(ε2qlnn) variation distance from exact oracles. Finally, we prove a lower bound of Ω(q⋅ε−2) oracle calls under a natural model of computation.
AU - Kolmogorov, Vladimir
ID - 274
T2 - Proceedings of the 31st Conference On Learning Theory
TI - A faster approximation algorithm for the Gibbs partition function
VL - 75
ER -
TY - THES
AB - The thesis encompasses several topics of plant cell biology which were studied in the model plant Arabidopsis thaliana. Chapter 1 concerns the plant hormone auxin and its polar transport through cells and tissues. The highly controlled, directional transport of auxin is facilitated by plasma membrane-localized transporters. Transporters from the PIN family direct auxin transport due to their polarized localizations at cell membranes. Substantial effort has been put into research on cellular trafficking of PIN proteins, which is thought to underlie their polar distribution. I participated in a forward genetic screen aimed at identifying novel regulators of PIN polarity. The screen yielded several genes which may be involved in PIN polarity regulation or participate in polar auxin transport by other means. Chapter 2 focuses on the endomembrane system, with particular attention to clathrin-mediated endocytosis. The project started with identification of several proteins that interact with clathrin light chains. Among them, I focused on two putative homologues of auxilin, which in non-plant systems is an endocytotic factor known for uncoating clathrin-coated vesicles in the final step of endocytosis. The body of my work consisted of an in-depth characterization of transgenic A. thaliana lines overexpressing these putative auxilins in an inducible manner. Overexpression of these proteins leads to an inhibition of endocytosis, as documented by imaging of cargoes and clathrin-related endocytic machinery. An extension of this work is an investigation into a concept of homeostatic regulation acting between distinct transport processes in the endomembrane system. With auxilin overexpressing lines, where endocytosis is blocked specifically, I made observations on the mutual relationship between two opposite trafficking processes of secretion and endocytosis. In Chapter 3, I analyze cortical microtubule arrays and their relationship to auxin signaling and polarized growth in elongating cells. In plants, microtubules are organized into arrays just below the plasma membrane, and it is thought that their function is to guide membrane-docked cellulose synthase complexes. These, in turn, influence cell wall structure and cell shape by directed deposition of cellulose fibres. In elongating cells, cortical microtubule arrays are able to reorient in relation to long cell axis, and these reorientations have been linked to cell growth and to signaling of growth-regulating factors such as auxin or light. In this chapter, I am addressing the causal relationship between microtubule array reorientation, growth, and auxin signaling. I arrive at a model where array reorientation is not guided by auxin directly, but instead is only controlled by growth, which, in turn, is regulated by auxin.
AU - Adamowski, Maciek
ID - 938
TI - Investigations into cell polarity and trafficking in the plant model Arabidopsis thaliana
ER -
TY - JOUR
AB - We reveal the existence of continuous families of guided single-mode solitons in planar waveguides with weakly nonlinear active core and absorbing boundaries. Stable propagation of TE and TM-polarized solitons is accompanied by attenuation of all other modes, i.e., the waveguide features properties of conservative and dissipative systems. If the linear spectrum of the waveguide possesses exceptional points, which occurs in the case of TM polarization, an originally focusing (defocusing) material nonlinearity may become effectively defocusing (focusing). This occurs due to the geometric phase of the carried eigenmode when the surface impedance encircles the exceptional point. In its turn, the change of the effective nonlinearity ensures the existence of dark (bright) solitons in spite of focusing (defocusing) Kerr nonlinearity of the core. The existence of an exceptional point can also result in anomalous enhancement of the effective nonlinearity. In terms of practical applications, the nonlinearity of the reported waveguide can be manipulated by controlling the properties of the absorbing cladding.
AU - Midya, Bikashkali
AU - Konotop, Vladimir
ID - 939
IS - 3
JF - Physical Review Letters
SN - 00319007
TI - Waveguides with absorbing boundaries: Nonlinearity controlled by an exceptional point and solitons
VL - 119
ER -
TY - CONF
AB - Recently there has been a proliferation of automated program repair (APR) techniques, targeting various programming languages. Such techniques can be generally classified into two families: syntactic- and semantics-based. Semantics-based APR, on which we focus, typically uses symbolic execution to infer semantic constraints and then program synthesis to construct repairs conforming to them. While syntactic-based APR techniques have been shown successful on bugs in real-world programs written in both C and Java, semantics-based APR techniques mostly target C programs. This leaves empirical comparisons of the APR families not fully explored, and developers without a Java-based semantics APR technique. We present JFix, a semantics-based APR framework that targets Java, and an associated Eclipse plugin. JFix is implemented atop Symbolic PathFinder, a well-known symbolic execution engine for Java programs. It extends one particular APR technique (Angelix), and is designed to be sufficiently generic to support a variety of such techniques. We demonstrate that semantics-based APR can indeed efficiently and effectively repair a variety of classes of bugs in large real-world Java programs. This supports our claim that the framework can both support developers seeking semantics-based repair of bugs in Java programs, as well as enable larger scale empirical studies comparing syntactic- and semantics-based APR targeting Java. The demonstration of our tool is available via the project website at: https://xuanbachle.github.io/semanticsrepair/
AU - Le, Xuan
AU - Chu, Duc Hiep
AU - Lo, David
AU - Le Goues, Claire
AU - Visser, Willem
ID - 941
T2 - Proceedings of the 26th ACM SIGSOFT International Symposium on Software Testing and Analysis
TI - JFIX: Semantics-based repair of Java programs via symbolic PathFinder
ER -
TY - CONF
AB - A notable class of techniques for automatic program repair is known as semantics-based. Such techniques, e.g., Angelix, infer semantic specifications via symbolic execution, and then use program synthesis to construct new code that satisfies those inferred specifications. However, the obtained specifications are naturally incomplete, leaving the synthesis engine with a difficult task of synthesizing a general solution from a sparse space of many possible solutions that are consistent with the provided specifications but that do not necessarily generalize. We present S3, a new repair synthesis engine that leverages programming-by-examples methodology to synthesize high-quality bug repairs. The novelty in S3 that allows it to tackle the sparse search space to create more general repairs is three-fold: (1) A systematic way to customize and constrain the syntactic search space via a domain-specific language, (2) An efficient enumeration-based search strategy over the constrained search space, and (3) A number of ranking features based on measures of the syntactic and semantic distances between candidate solutions and the original buggy program. We compare S3’s repair effectiveness with state-of-the-art synthesis engines Angelix, Enumerative, and CVC4. S3 can successfully and correctly fix at least three times more bugs than the best baseline on datasets of 52 bugs in small programs, and 100 bugs in real-world large programs.
AU - Le, Xuan
AU - Chu, Duc Hiep
AU - Lo, David
AU - Le Goues, Claire
AU - Visser, Willem
ID - 942
SN - 978-145035105-8
TI - S3: Syntax- and semantic-guided repair synthesis via programming by examples
VL - F130154
ER -
TY - JOUR
AB - Like many developing tissues, the vertebrate neural tube is patterned by antiparallel morphogen gradients. To understand how these inputs are interpreted, we measured morphogen signaling and target gene expression in mouse embryos and chick ex vivo assays. From these data, we derived and validated a characteristic decoding map that relates morphogen input to the positional identity of neural progenitors. Analysis of the observed responses indicates that the underlying interpretation strategy minimizes patterning errors in response to the joint input of noisy opposing gradients. We reverse-engineered a transcriptional network that provides a mechanistic basis for the observed cell fate decisions and accounts for the precision and dynamics of pattern formation. Together, our data link opposing gradient dynamics in a growing tissue to precise pattern formation.
AU - Zagórski, Marcin P
AU - Tabata, Yoji
AU - Brandenberg, Nathalie
AU - Lutolf, Matthias
AU - Tkacik, Gasper
AU - Bollenbach, Tobias
AU - Briscoe, James
AU - Kicheva, Anna
ID - 943
IS - 6345
JF - Science
SN - 00368075
TI - Decoding of position in the developing neural tube from antiparallel morphogen gradients
VL - 356
ER -
TY - JOUR
AB - The concerted production of neurons and glia by neural stem cells (NSCs) is essential for neural circuit assembly. In the developing cerebral cortex, radial glia progenitors (RGPs) generate nearly all neocortical neurons and certain glia lineages. RGP proliferation behavior shows a high degree of non-stochasticity, thus a deterministic characteristic of neuron and glia production. However, the cellular and molecular mechanisms controlling RGP behavior and proliferation dynamics in neurogenesis and glia generation remain unknown. By using mosaic analysis with double markers (MADM)-based genetic paradigms enabling the sparse and global knockout with unprecedented single-cell resolution, we identified Lgl1 as a critical regulatory component. We uncover Lgl1-dependent tissue-wide community effects required for embryonic cortical neurogenesis and novel cell-autonomous Lgl1 functions controlling RGP-mediated glia genesis and postnatal NSC behavior. These results suggest that NSC-mediated neuron and glia production is tightly regulated through the concerted interplay of sequential Lgl1-dependent global and cell intrinsic mechanisms.
AU - Beattie, Robert J
AU - Postiglione, Maria P
AU - Burnett, Laura
AU - Laukoter, Susanne
AU - Streicher, Carmen
AU - Pauler, Florian
AU - Xiao, Guanxi
AU - Klezovitch, Olga
AU - Vasioukhin, Valeri
AU - Ghashghaei, Troy
AU - Hippenmeyer, Simon
ID - 944
IS - 3
JF - Neuron
SN - 08966273
TI - Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells
VL - 94
ER -
TY - JOUR
AB - While chromosome-wide dosage compensation of the X chromosome has been found in many species, studies in ZW clades have indicated that compensation of the Z is more localized and/or incomplete. In the ZW Lepidoptera, some species show complete compensation of the Z chromosome, while others lack full equalization, but what drives these inconsistencies is unclear. Here, we compare patterns of male and female gene expression on the Z chromosome of two closely related butterfly species, Papilio xuthus and Papilio machaon, and in multiple tissues of two moths species, Plodia interpunctella and Bombyx mori, which were previously found to differ in the extent to which they equalize Z-linked gene expression between the sexes. We find that, while some species and tissues seem to have incomplete dosage compensation, this is in fact due to the accumulation of male-biased genes and the depletion of female-biased genes on the Z chromosome. Once this is accounted for, the Z chromosome is fully compensated in all four species, through the up-regulation of Z expression in females and in some cases additional down-regulation in males. We further find that both sex-biased genes and Z-linked genes have increased rates of expression divergence in this clade, and that this can lead to fast shifts in patterns of gene expression even between closely related species. Taken together, these results show that the uneven distribution of sex-biased genes on sex chromosomes can confound conclusions about dosage compensation and that Z chromosome-wide dosage compensation is not only possible but ubiquitous among Lepidoptera.
AU - Huylmans, Ann K
AU - Macon, Ariana
AU - Vicoso, Beatriz
ID - 945
IS - 10
JF - Molecular Biology and Evolution
SN - 07374038
TI - Global dosage compensation is ubiquitous in Lepidoptera, but counteracted by the masculinization of the Z chromosome
VL - 34
ER -
TY - JOUR
AB - Roots navigate through soil integrating environmental signals to orient their growth. The Arabidopsis root is a widely used model for developmental, physiological and cell biological studies. Live imaging greatly aids these efforts, but the horizontal sample position and continuous root tip displacement present significant difficulties. Here, we develop a confocal microscope setup for vertical sample mounting and integrated directional illumination. We present TipTracker – a custom software for automatic tracking of diverse moving objects usable on various microscope setups. Combined, this enables observation of root tips growing along the natural gravity vector over prolonged periods of time, as well as the ability to induce rapid gravity or light stimulation. We also track migrating cells in the developing zebrafish embryo, demonstrating the utility of this system in the acquisition of high-resolution data sets of dynamic samples. We provide detailed descriptions of the tools enabling the easy implementation on other microscopes.
AU - Von Wangenheim, Daniel
AU - Hauschild, Robert
AU - Fendrych, Matyas
AU - Barone, Vanessa
AU - Benková, Eva
AU - Friml, Jirí
ID - 946
JF - eLife
TI - Live tracking of moving samples in confocal microscopy for vertically grown roots
VL - 6
ER -
TY - JOUR
AB - Viewing the ways a living cell can organize its metabolism as the phase space of a physical system, regulation can be seen as the ability to reduce the entropy of that space by selecting specific cellular configurations that are, in some sense, optimal. Here we quantify the amount of regulation required to control a cell's growth rate by a maximum-entropy approach to the space of underlying metabolic phenotypes, where a configuration corresponds to a metabolic flux pattern as described by genome-scale models. We link the mean growth rate achieved by a population of cells to the minimal amount of metabolic regulation needed to achieve it through a phase diagram that highlights how growth suppression can be as costly (in regulatory terms) as growth enhancement. Moreover, we provide an interpretation of the inverse temperature β controlling maximum-entropy distributions based on the underlying growth dynamics. Specifically, we show that the asymptotic value of β for a cell population can be expected to depend on (i) the carrying capacity of the environment, (ii) the initial size of the colony, and (iii) the probability distribution from which the inoculum was sampled. Results obtained for E. coli and human cells are found to be remarkably consistent with empirical evidence.
AU - De Martino, Daniele
AU - Capuani, Fabrizio
AU - De Martino, Andrea
ID - 947
IS - 1
JF - Physical Review E Statistical Nonlinear and Soft Matter Physics
SN - 24700045
TI - Quantifying the entropic cost of cellular growth control
VL - 96
ER -
TY - CONF
AB - Two-player games on graphs are widely studied in formal methods as they model the interaction between a system and its environment. The game is played by moving a token throughout a graph to produce an infinite path. There are several common modes to determine how the players move the token through the graph; e.g., in turn-based games the players alternate turns in moving the token. We study the bidding mode of moving the token, which, to the best of our knowledge, has never been studied in infinite-duration games. Both players have separate budgets, which sum up to $1$. In each turn, a bidding takes place. Both players submit bids simultaneously, and a bid is legal if it does not exceed the available budget. The winner of the bidding pays his bid to the other player and moves the token. For reachability objectives, repeated bidding games have been studied and are called Richman games. There, a central question is the existence and computation of threshold budgets; namely, a value t\in [0,1] such that if\PO's budget exceeds $t$, he can win the game, and if\PT's budget exceeds 1-t, he can win the game. We focus on parity games and mean-payoff games. We show the existence of threshold budgets in these games, and reduce the problem of finding them to Richman games. We also determine the strategy-complexity of an optimal strategy. Our most interesting result shows that memoryless strategies suffice for mean-payoff bidding games.
AU - Avni, Guy
AU - Henzinger, Thomas A
AU - Chonev, Ventsislav K
ID - 950
SN - 1868-8969
TI - Infinite-duration bidding games
VL - 85
ER -
TY - JOUR
AB - Dengue-suppressing Wolbachia strains are promising tools for arbovirus control, particularly as they have the potential to self-spread following local introductions. To test this, we followed the frequency of the transinfected Wolbachia strain wMel through Ae. aegypti in Cairns, Australia, following releases at 3 nonisolated locations within the city in early 2013. Spatial spread was analysed graphically using interpolation and by fitting a statistical model describing the position and width of the wave. For the larger 2 of the 3 releases (covering 0.97 km2 and 0.52 km2), we observed slow but steady spatial spread, at about 100–200 m per year, roughly consistent with theoretical predictions. In contrast, the smallest release (0.11 km2) produced erratic temporal and spatial dynamics, with little evidence of spread after 2 years. This is consistent with the prediction concerning fitness-decreasing Wolbachia transinfections that a minimum release area is needed to achieve stable local establishment and spread in continuous habitats. Our graphical and likelihood analyses produced broadly consistent estimates of wave speed and wave width. Spread at all sites was spatially heterogeneous, suggesting that environmental heterogeneity will affect large-scale Wolbachia transformations of urban mosquito populations. The persistence and spread of Wolbachia in release areas meeting minimum area requirements indicates the promise of successful large-scale population transfo
AU - Schmidt, Tom
AU - Barton, Nicholas H
AU - Rasic, Gordana
AU - Turley, Andrew
AU - Montgomery, Brian
AU - Iturbe Ormaetxe, Inaki
AU - Cook, Peter
AU - Ryan, Peter
AU - Ritchie, Scott
AU - Hoffmann, Ary
AU - O’Neill, Scott
AU - Turelli, Michael
ID - 951
IS - 5
JF - PLoS Biology
SN - 15449173
TI - Local introduction and heterogeneous spatial spread of dengue-suppressing Wolbachia through an urban population of Aedes Aegypti
VL - 15
ER -
TY - JOUR
AB - A novel strategy for controlling the spread of arboviral diseases such as dengue, Zika and chikungunya is to transform mosquito populations with virus-suppressing Wolbachia. In general, Wolbachia transinfected into mosquitoes induce fitness costs through lower viability or fecundity. These maternally inherited bacteria also produce a frequency-dependent advantage for infected females by inducing cytoplasmic incompatibility (CI), which kills the embryos produced by uninfected females mated to infected males. These competing effects, a frequency-dependent advantage and frequency-independent costs, produce bistable Wolbachia frequency dynamics. Above a threshold frequency, denoted pˆ, CI drives fitness-decreasing Wolbachia transinfections through local populations; but below pˆ, infection frequencies tend to decline to zero. If pˆ is not too high, CI also drives spatial spread once infections become established over sufficiently large areas. We illustrate how simple models provide testable predictions concerning the spatial and temporal dynamics of Wolbachia introductions, focusing on rate of spatial spread, the shape of spreading waves, and the conditions for initiating spread from local introductions. First, we consider the robustness of diffusion-based predictions to incorporating two important features of wMel-Aedes aegypti biology that may be inconsistent with the diffusion approximations, namely fast local dynamics induced by complete CI (i.e., all embryos produced from incompatible crosses die) and long-tailed, non-Gaussian dispersal. With complete CI, our numerical analyses show that long-tailed dispersal changes wave-width predictions only slightly; but it can significantly reduce wave speed relative to the diffusion prediction; it also allows smaller local introductions to initiate spatial spread. Second, we use approximations for pˆ and dispersal distances to predict the outcome of 2013 releases of wMel-infected Aedes aegypti in Cairns, Australia, Third, we describe new data from Ae. aegypti populations near Cairns, Australia that demonstrate long-distance dispersal and provide an approximate lower bound on pˆ for wMel in northeastern Australia. Finally, we apply our analyses to produce operational guidelines for efficient transformation of vector populations over large areas. We demonstrate that even very slow spatial spread, on the order of 10-20 m/month (as predicted), can produce area-wide population transformation within a few years following initial releases covering about 20-30% of the target area.
AU - Turelli, Michael
AU - Barton, Nicholas H
ID - 952
JF - Theoretical Population Biology
SN - 00405809
TI - Deploying dengue-suppressing Wolbachia: Robust models predict slow but effective spatial spread in Aedes aegypti
VL - 115
ER -
TY - JOUR
AB - The role of natural selection in the evolution of adaptive phenotypes has undergone constant probing by evolutionary biologists, employing both theoretical and empirical approaches. As Darwin noted, natural selection can act together with other processes, including random changes in the frequencies of phenotypic differences that are not under strong selection, and changes in the environment, which may reflect evolutionary changes in the organisms themselves. As understanding of genetics developed after 1900, the new genetic discoveries were incorporated into evolutionary biology. The resulting general principles were summarized by Julian Huxley in his 1942 book Evolution: the modern synthesis. Here, we examine how recent advances in genetics, developmental biology and molecular biology, including epigenetics, relate to today's understanding of the evolution of adaptations. We illustrate how careful genetic studies have repeatedly shown that apparently puzzling results in a wide diversity of organisms involve processes that are consistent with neo-Darwinism. They do not support important roles in adaptation for processes such as directed mutation or the inheritance of acquired characters, and therefore no radical revision of our understanding of the mechanism of adaptive evolution is needed.
AU - Charlesworth, Deborah
AU - Barton, Nicholas H
AU - Charlesworth, Brian
ID - 953
IS - 1855
JF - Proceedings of the Royal Society of London Series B Biological Sciences
TI - The sources of adaptive evolution
VL - 284
ER -
TY - JOUR
AB - Understanding the relation between genotype and phenotype remains a major challenge. The difficulty of predicting individual mutation effects, and particularly the interactions between them, has prevented the development of a comprehensive theory that links genotypic changes to their phenotypic effects. We show that a general thermodynamic framework for gene regulation, based on a biophysical understanding of protein-DNA binding, accurately predicts the sign of epistasis in a canonical cis-regulatory element consisting of overlapping RNA polymerase and repressor binding sites. Sign and magnitude of individual mutation effects are sufficient to predict the sign of epistasis and its environmental dependence. Thus, the thermodynamic model offers the correct null prediction for epistasis between mutations across DNA-binding sites. Our results indicate that a predictive theory for the effects of cis-regulatory mutations is possible from first principles, as long as the essential molecular mechanisms and the constraints these impose on a biological system are accounted for.
AU - Lagator, Mato
AU - Paixao, Tiago
AU - Barton, Nicholas H
AU - Bollback, Jonathan P
AU - Guet, Calin C
ID - 954
JF - eLife
SN - 2050084X
TI - On the mechanistic nature of epistasis in a canonical cis-regulatory element
VL - 6
ER -
TY - JOUR
AB - Gene expression is controlled by networks of regulatory proteins that interact specifically with external signals and DNA regulatory sequences. These interactions force the network components to co-evolve so as to continually maintain function. Yet, existing models of evolution mostly focus on isolated genetic elements. In contrast, we study the essential process by which regulatory networks grow: the duplication and subsequent specialization of network components. We synthesize a biophysical model of molecular interactions with the evolutionary framework to find the conditions and pathways by which new regulatory functions emerge. We show that specialization of new network components is usually slow, but can be drastically accelerated in the presence of regulatory crosstalk and mutations that promote promiscuous interactions between network components.
AU - Friedlander, Tamar
AU - Prizak, Roshan
AU - Barton, Nicholas H
AU - Tkacik, Gasper
ID - 955
IS - 1
JF - Nature Communications
SN - 20411723
TI - Evolution of new regulatory functions on biophysically realistic fitness landscapes
VL - 8
ER -
TY - JOUR
AB - We study a class of ergodic quantum Markov semigroups on finite-dimensional unital C⁎-algebras. These semigroups have a unique stationary state σ, and we are concerned with those that satisfy a quantum detailed balance condition with respect to σ. We show that the evolution on the set of states that is given by such a quantum Markov semigroup is gradient flow for the relative entropy with respect to σ in a particular Riemannian metric on the set of states. This metric is a non-commutative analog of the 2-Wasserstein metric, and in several interesting cases we are able to show, in analogy with work of Otto on gradient flows with respect to the classical 2-Wasserstein metric, that the relative entropy is strictly and uniformly convex with respect to the Riemannian metric introduced here. As a consequence, we obtain a number of new inequalities for the decay of relative entropy for ergodic quantum Markov semigroups with detailed balance.
AU - Carlen, Eric
AU - Maas, Jan
ID - 956
IS - 5
JF - Journal of Functional Analysis
SN - 00221236
TI - Gradient flow and entropy inequalities for quantum Markov semigroups with detailed balance
VL - 273
ER -
TY - CHAP
AB - Small molecule biosensors based on Forster resonance energy transfer (FRET) enable small molecule signaling to be monitored with high spatial and temporal resolution in complex cellular environments. FRET sensors can be constructed by fusing a pair of fluorescent proteins to a suitable recognition domain, such as a member of the solute-binding protein (SBP) superfamily. However, naturally occurring SBPs may be unsuitable for incorporation into FRET sensors due to their low thermostability, which may preclude imaging under physiological conditions, or because the positions of their N- and C-termini may be suboptimal for fusion of fluorescent proteins, which may limit the dynamic range of the resulting sensors. Here, we show how these problems can be overcome using ancestral protein reconstruction and circular permutation. Ancestral protein reconstruction, used as a protein engineering strategy, leverages phylogenetic information to improve the thermostability of proteins, while circular permutation enables the termini of an SBP to be repositioned to maximize the dynamic range of the resulting FRET sensor. We also provide a protocol for cloning the engineered SBPs into FRET sensor constructs using Golden Gate assembly and discuss considerations for in situ characterization of the FRET sensors.
AU - Clifton, Ben
AU - Whitfield, Jason
AU - Sanchez Romero, Inmaculada
AU - Herde, Michel
AU - Henneberger, Christian
AU - Janovjak, Harald L
AU - Jackson, Colin
ED - Stein, Viktor
ID - 957
SN - 10643745
T2 - Synthetic Protein Switches
TI - Ancestral protein reconstruction and circular permutation for improving the stability and dynamic range of FRET sensors
VL - 1596
ER -
TY - CHAP
AB - Biosensors that exploit Forster resonance energy transfer (FRET) can be used to visualize biological and physiological processes and are capable of providing detailed information in both spatial and temporal dimensions. In a FRET-based biosensor, substrate binding is associated with a change in the relative positions of two fluorophores, leading to a change in FRET efficiency that may be observed in the fluorescence spectrum. As a result, their design requires a ligand-binding protein that exhibits a conformational change upon binding. However, not all ligand-binding proteins produce responsive sensors upon conjugation to fluorescent proteins or dyes, and identifying the optimum locations for the fluorophores often involves labor-intensive iterative design or high-throughput screening. Combining the genetic fusion of a fluorescent protein to the ligand-binding protein with site-specific covalent attachment of a fluorescent dye can allow fine control over the positions of the two fluorophores, allowing the construction of very sensitive sensors. This relies upon the accurate prediction of the locations of the two fluorophores in bound and unbound states. In this chapter, we describe a method for computational identification of dye-attachment sites that allows the use of cysteine modification to attach synthetic dyes that can be paired with a fluorescent protein for the purposes of creating FRET sensors.
AU - Mitchell, Joshua
AU - Zhang, William
AU - Herde, Michel
AU - Henneberger, Christian
AU - Janovjak, Harald L
AU - O'Mara, Megan
AU - Jackson, Colin
ED - Stein, Viktor
ID - 958
SN - 10643745
T2 - Synthetic Protein Switches
TI - Method for developing optical sensors using a synthetic dye fluorescent protein FRET pair and computational modeling and assessment
VL - 1596
ER -
TY - JOUR
AB - In this work it is shown that scale-free tails in metabolic flux distributions inferred in stationary models are an artifact due to reactions involved in thermodynamically unfeasible cycles, unbounded by physical constraints and in principle able to perform work without expenditure of free energy. After implementing thermodynamic constraints by removing such loops, metabolic flux distributions scale meaningfully with the physical limiting factors, acquiring in turn a richer multimodal structure potentially leading to symmetry breaking while optimizing for objective functions.
AU - De Martino, Daniele
ID - 959
IS - 6
JF - Physical Review E Statistical Nonlinear and Soft Matter Physics
SN - 24700045
TI - Scales and multimodal flux distributions in stationary metabolic network models via thermodynamics
VL - 95
ER -
TY - CONF
AB - We present a new algorithm for model counting of a class of string constraints. In addition to the classic operation of concatenation, our class includes some recursively defined operations such as Kleene closure, and replacement of substrings. Additionally, our class also includes length constraints on the string expressions, which means, by requiring reasoning about numbers, that we face a multi-sorted logic. In the end, our string constraints are motivated by their use in programming for web applications. Our algorithm comprises two novel features: the ability to use a technique of (1) partial derivatives for constraints that are already in a solved form, i.e. a form where its (string) satisfiability is clearly displayed, and (2) non-progression, where cyclic reasoning in the reduction process may be terminated (thus allowing for the algorithm to look elsewhere). Finally, we experimentally compare our model counter with two recent works on model counting of similar constraints, SMC [18] and ABC [5], to demonstrate its superior performance.
AU - Trinh, Minh
AU - Chu, Duc Hiep
AU - Jaffar, Joxan
ED - Majumdar, Rupak
ED - Kunčak, Viktor
ID - 962
SN - 03029743
TI - Model counting for recursively-defined strings
VL - 10427
ER -
TY - CONF
AB - Network games are widely used as a model for selfish resource-allocation problems. In the classical model, each player selects a path connecting her source and target vertex. The cost of traversing an edge depends on the number of players that traverse it. Thus, it abstracts the fact that different users may use a resource at different times and for different durations, which plays an important role in defining the costs of the users in reality. For example, when transmitting packets in a communication network, routing traffic in a road network, or processing a task in a production system, the traversal of the network involves an inherent delay, and so sharing and congestion of resources crucially depends on time. We study timed network games , which add a time component to network games. Each vertex v in the network is associated with a cost function, mapping the load on v to the price that a player pays for staying in v for one time unit with this load. In addition, each edge has a guard, describing time intervals in which the edge can be traversed, forcing the players to spend time on vertices. Unlike earlier work that add a time component to network games, the time in our model is continuous and cannot be discretized. In particular, players have uncountably many strategies, and a game may have uncountably many pure Nash equilibria. We study properties of timed network games with cost-sharing or congestion cost functions: their stability, equilibrium inefficiency, and complexity. In particular, we show that the answer to the question whether we can restrict attention to boundary strategies, namely ones in which edges are traversed only at the boundaries of guards, is mixed.
AU - Avni, Guy
AU - Guha, Shibashis
AU - Kupferman, Orna
ID - 963
SN - 18688969
TI - Timed network games with clocks
VL - 83
ER -
TY - GEN
AU - Nikolic, Nela
AU - Schreiber, Frank
AU - Dal Co, Alma
AU - Kiviet, Daniel
AU - Bergmiller, Tobias
AU - Littmann, Sten
AU - Kuypers, Marcel
AU - Ackermann, Martin
ID - 9844
TI - Source data for figures and tables
ER -
TY - GEN
AB - Estimates of 13 C-arabinose and 2 H-glucose uptake from the fractions of heavy isotopes measured in single cells
AU - Nikolic, Nela
AU - Schreiber, Frank
AU - Dal Co, Alma
AU - Kiviet, Daniel
AU - Bergmiller, Tobias
AU - Littmann, Sten
AU - Kuypers, Marcel
AU - Ackermann, Martin
ID - 9845
TI - Mathematical model
ER -
TY - GEN
AU - Nikolic, Nela
AU - Schreiber, Frank
AU - Dal Co, Alma
AU - Kiviet, Daniel
AU - Bergmiller, Tobias
AU - Littmann, Sten
AU - Kuypers, Marcel
AU - Ackermann, Martin
ID - 9846
TI - Supplementary methods
ER -
TY - GEN
AB - This text provides additional information about the model, a derivation of the analytic results in Eq (4), and details about simulations of an additional parameter set.
AU - Lukacisinova, Marta
AU - Novak, Sebastian
AU - Paixao, Tiago
ID - 9849
TI - Modelling and simulation details
ER -
TY - GEN
AB - In this text, we discuss how a cost of resistance and the possibility of lethal mutations impact our model.
AU - Lukacisinova, Marta
AU - Novak, Sebastian
AU - Paixao, Tiago
ID - 9850
TI - Extensions of the model
ER -
TY - GEN
AB - Based on the intuitive derivation of the dynamics of SIM allele frequency pM in the main text, we present a heuristic prediction for the long-term SIM allele frequencies with χ > 1 stresses and compare it to numerical simulations.
AU - Lukacisinova, Marta
AU - Novak, Sebastian
AU - Paixao, Tiago
ID - 9851
TI - Heuristic prediction for multiple stresses
ER -
TY - GEN
AB - We show how different combination strategies affect the fraction of individuals that are multi-resistant.
AU - Lukacisinova, Marta
AU - Novak, Sebastian
AU - Paixao, Tiago
ID - 9852
TI - Resistance frequencies for different combination strategies
ER -
TY - GEN
AB - Includes derivation of optimal estimation algorithm, generalisation to non-poisson noise statistics, correlated input noise, and implementation of in a multi-layer neural network.
AU - Chalk, Matthew J
AU - Masset, Paul
AU - Gutkin, Boris
AU - Denève, Sophie
ID - 9855
TI - Supplementary appendix
ER -
TY - GEN
AU - Schmidt, Tom
AU - Barton, Nicholas H
AU - Rasic, Gordana
AU - Turley, Andrew
AU - Montgomery, Brian
AU - Iturbe Ormaetxe, Inaki
AU - Cook, Peter
AU - Ryan, Peter
AU - Ritchie, Scott
AU - Hoffmann, Ary
AU - O’Neill, Scott
AU - Turelli, Michael
ID - 9856
TI - Supporting Information concerning additional likelihood analyses and results
ER -
TY - GEN
AU - Schmidt, Tom
AU - Barton, Nicholas H
AU - Rasic, Gordana
AU - Turley, Andrew
AU - Montgomery, Brian
AU - Iturbe Ormaetxe, Inaki
AU - Cook, Peter
AU - Ryan, Peter
AU - Ritchie, Scott
AU - Hoffmann, Ary
AU - O’Neill, Scott
AU - Turelli, Michael
ID - 9857
TI - Supporting information concerning observed wMel frequencies and analyses of habitat variables
ER -
TY - GEN
AU - Schmidt, Tom
AU - Barton, Nicholas H
AU - Rasic, Gordana
AU - Turley, Andrew
AU - Montgomery, Brian
AU - Iturbe Ormaetxe, Inaki
AU - Cook, Peter
AU - Ryan, Peter
AU - Ritchie, Scott
AU - Hoffmann, Ary
AU - O’Neill, Scott
AU - Turelli, Michael
ID - 9858
TI - Excel file with data on mosquito densities, Wolbachia infection status and housing characteristics
ER -
TY - JOUR
AB - The current-phase relation (CPR) of a Josephson junction (JJ) determines how the supercurrent evolves with the superconducting phase difference across the junction. Knowledge of the CPR is essential in order to understand the response of a JJ to various external parameters. Despite the rising interest in ultraclean encapsulated graphene JJs, the CPR of such junctions remains unknown. Here, we use a fully gate-tunable graphene superconducting quantum intereference device (SQUID) to determine the CPR of ballistic graphene JJs. Each of the two JJs in the SQUID is made with graphene encapsulated in hexagonal boron nitride. By independently controlling the critical current of the JJs, we can operate the SQUID either in a symmetric or asymmetric configuration. The highly asymmetric SQUID allows us to phase-bias one of the JJs and thereby directly obtain its CPR. The CPR is found to be skewed, deviating significantly from a sinusoidal form. The skewness can be tuned with the gate voltage and oscillates in antiphase with Fabry-Pérot resistance oscillations of the ballistic graphene cavity. We compare our experiments with tight-binding calculations that include realistic graphene-superconductor interfaces and find a good qualitative agreement.
AU - Nanda, Gaurav
AU - Aguilera Servin, Juan L
AU - Rakyta, Péter
AU - Kormányos, Andor
AU - Kleiner, Reinhold
AU - Koelle, Dieter
AU - Watanabe, Kazuo
AU - Taniguchi, Takashi
AU - Vandersypen, Lieven
AU - Goswami, Srijit
ID - 988
IS - 6
JF - Nano Letters
SN - 15306984
TI - Current-phase relation of ballistic graphene Josephson junctions
VL - 17
ER -
TY - CONF
AB - We present a generalized optimal transport model in which the mass-preserving constraint for the L2-Wasserstein distance is relaxed by introducing a source term in the continuity equation. The source term is also incorporated in the path energy by means of its squared L2-norm in time of a functional with linear growth in space. This extension of the original transport model enables local density modulations, which is a desirable feature in applications such as image warping and blending. A key advantage of the use of a functional with linear growth in space is that it allows for singular sources and sinks, which can be supported on points or lines. On a technical level, the L2-norm in time ensures a disintegration of the source in time, which we use to obtain the well-posedness of the model and the existence of geodesic paths. The numerical discretization is based on the proximal splitting approach [18] and selected numerical test cases show the potential of the proposed approach. Furthermore, the approach is applied to the warping and blending of textures.
AU - Maas, Jan
AU - Rumpf, Martin
AU - Simon, Stefan
ED - Lauze, François
ED - Dong, Yiqiu
ED - Bjorholm Dahl, Anders
ID - 989
SN - 03029743
TI - Transport based image morphing with intensity modulation
VL - 10302
ER -
TY - JOUR
AB - Assortative mating is an important driver of speciation in populations with gene flow and is predicted to evolve under certain conditions in few-locus models. However, the evolution of assortment is less understood for mating based on quantitative traits, which are often characterized by high genetic variability and extensive linkage disequilibrium between trait loci. We explore this scenario for a two-deme model with migration, by considering a single polygenic trait subject to divergent viability selection across demes, as well as assortative mating and sexual selection within demes, and investigate how trait divergence is shaped by various evolutionary forces. Our analysis reveals the existence of sharp thresholds of assortment strength, at which divergence increases dramatically. We also study the evolution of assortment via invasion of modifiers of mate discrimination and show that the ES assortment strength has an intermediate value under a range of migration-selection parameters, even in diverged populations, due to subtle effects which depend sensitively on the extent of phenotypic variation within these populations. The evolutionary dynamics of the polygenic trait is studied using the hypergeometric and infinitesimal models. We further investigate the sensitivity of our results to the assumptions of the hypergeometric model, using individual-based simulations.
AU - Sachdeva, Himani
AU - Barton, Nicholas H
ID - 990
IS - 6
JF - Evolution; International Journal of Organic Evolution
SN - 00143820
TI - Divergence and evolution of assortative mating in a polygenic trait model of speciation with gene flow
VL - 71
ER -
TY - JOUR
AB - Synaptotagmin 7 (Syt7) was originally identified as a slow Ca2+ sensor for lysosome fusion, but its function at fast synapses is controversial. The paper by Luo and Südhof (2017) in this issue of Neuron shows that at the calyx of Held in the auditory brainstem Syt7 triggers asynchronous release during stimulus trains, resulting in reliable and temporally precise high-frequency transmission. Thus, a slow Ca2+ sensor contributes to the fast signaling properties of the calyx synapse.
AU - Chen, Chong
AU - Jonas, Peter M
ID - 991
IS - 4
JF - Neuron
SN - 08966273
TI - Synaptotagmins: That’s why so many
VL - 94
ER -
TY - THES
AB - An instance of the Constraint Satisfaction Problem (CSP) is given by a finite set of
variables, a finite domain of labels, and a set of constraints, each constraint acting on
a subset of the variables. The goal is to find an assignment of labels to its variables
that satisfies all constraints (or decide whether one exists). If we allow more general
“soft” constraints, which come with (possibly infinite) costs of particular assignments,
we obtain instances from a richer class called Valued Constraint Satisfaction Problem
(VCSP). There the goal is to find an assignment with minimum total cost.
In this thesis, we focus (assuming that P
6
=
NP) on classifying computational com-
plexity of CSPs and VCSPs under certain restricting conditions. Two results are the core
content of the work. In one of them, we consider VCSPs parametrized by a constraint
language, that is the set of “soft” constraints allowed to form the instances, and finish
the complexity classification modulo (missing pieces of) complexity classification for
analogously parametrized CSP. The other result is a generalization of Edmonds’ perfect
matching algorithm. This generalization contributes to complexity classfications in two
ways. First, it gives a new (largest known) polynomial-time solvable class of Boolean
CSPs in which every variable may appear in at most two constraints and second, it
settles full classification of Boolean CSPs with planar drawing (again parametrized by a
constraint language).
AU - Rolinek, Michal
ID - 992
TI - Complexity of constraint satisfaction
ER -
TY - JOUR
AB - In real-world applications, observations are often constrained to a small fraction of a system. Such spatial subsampling can be caused by the inaccessibility or the sheer size of the system, and cannot be overcome by longer sampling. Spatial subsampling can strongly bias inferences about a system’s aggregated properties. To overcome the bias, we derive analytically a subsampling scaling framework that is applicable to different observables, including distributions of neuronal avalanches, of number of people infected during an epidemic outbreak, and of node degrees. We demonstrate how to infer the correct distributions of the underlying full system, how to apply it to distinguish critical from subcritical systems, and how to disentangle subsampling and finite size effects. Lastly, we apply subsampling scaling to neuronal avalanche models and to recordings from developing neural networks. We show that only mature, but not young networks follow power-law scaling, indicating self-organization to criticality during development.
AU - Levina (Martius), Anna
AU - Priesemann, Viola
ID - 993
JF - Nature Communications
SN - 20411723
TI - Subsampling scaling
VL - 8
ER -
TY - JOUR
AB - The formation of vortices is usually considered to be the main mechanism of angular momentum disposal in superfluids. Recently, it was predicted that a superfluid can acquire angular momentum via an alternative, microscopic route -- namely, through interaction with rotating impurities, forming so-called `angulon quasiparticles' [Phys. Rev. Lett. 114, 203001 (2015)]. The angulon instabilities correspond to transfer of a small number of angular momentum quanta from the impurity to the superfluid, as opposed to vortex instabilities, where angular momentum is quantized in units of ℏ per atom. Furthermore, since conventional impurities (such as molecules) represent three-dimensional (3D) rotors, the angular momentum transferred is intrinsically 3D as well, as opposed to a merely planar rotation which is inherent to vortices. Herein we show that the angulon theory can explain the anomalous broadening of the spectroscopic lines observed for CH 3 and NH 3 molecules in superfluid helium nanodroplets, thereby providing a fingerprint of the emerging angulon instabilities in experiment.
AU - Cherepanov, Igor
AU - Lemeshko, Mikhail
ID - 994
IS - 3
JF - Physical Review Materials
TI - Fingerprints of angulon instabilities in the spectra of matrix-isolated molecules
VL - 1
ER -
TY - JOUR
AB - Recently it was shown that an impurity exchanging orbital angular momentum with a surrounding bath can be described in terms of the angulon quasiparticle [Phys. Rev. Lett. 118, 095301 (2017)]. The angulon consists of a quantum rotor dressed by a many-particle field of boson excitations, and can be formed out of, for example, a molecule or a nonspherical atom in superfluid helium, or out of an electron coupled to lattice phonons or a Bose condensate. Here we develop an approach to the angulon based on the path-integral formalism, which sets the ground for a systematic, perturbative treatment of the angulon problem. The resulting perturbation series can be interpreted in terms of Feynman diagrams, from which, in turn, one can derive a set of diagrammatic rules. These rules extend the machinery of the graphical theory of angular momentum - well known from theoretical atomic spectroscopy - to the case where an environment with an infinite number of degrees of freedom is present. In particular, we show that each diagram can be interpreted as a 'skeleton', which enforces angular momentum conservation, dressed by an additional many-body contribution. This connection between the angulon theory and the graphical theory of angular momentum is particularly important as it allows to systematically and substantially simplify the analytical representation of each diagram. In order to exemplify the technique, we calculate the 1- and 2-loop contributions to the angulon self-energy, the spectral function, and the quasiparticle weight. The diagrammatic theory we develop paves the way to investigate next-to-leading order quantities in a more compact way compared to the variational approaches.
AU - Bighin, Giacomo
AU - Lemeshko, Mikhail
ID - 995
IS - 8
JF - Physical Review B - Condensed Matter and Materials Physics
SN - 24699950
TI - Diagrammatic approach to orbital quantum impurities interacting with a many-particle environment
VL - 96
ER -
TY - JOUR
AB - Iodine (I 2 ) molecules embedded in He nanodroplets are aligned by a 160 ps long laser pulse. The highest degree of alignment, occurring at the peak of the pulse and quantified by ⟨cos 2 θ 2D ⟩ , is measured as a function of the laser intensity. The results are well described by ⟨cos 2 θ 2D ⟩ calculated for a gas of isolated molecules each with an effective rotational constant of 0.6 times the gas-phase value, and at a temperature of 0.4 K. Theoretical analysis using the angulon quasiparticle to describe rotating molecules in superfluid helium rationalizes why the alignment mechanism is similar to that of isolated molecules with an effective rotational constant. A major advantage of molecules in He droplets is that their 0.4 K temperature leads to stronger alignment than what can generally be achieved for gas phase molecules -- here demonstrated by a direct comparison of the droplet results to measurements on a ∼ 1 K supersonic beam of isolated molecules. This point is further illustrated for more complex system by measurements on 1,4-diiodobenzene and 1,4-dibromobenzene. For all three molecular species studied the highest values of ⟨cos 2 θ 2D ⟩ achieved in He droplets exceed 0.96.
AU - Shepperson, Benjamin
AU - Chatterley, Adam
AU - Søndergaard, Anders
AU - Christiansen, Lars
AU - Lemeshko, Mikhail
AU - Stapelfeldt, Henrik
ID - 996
IS - 1
JF - The Journal of Chemical Physics
SN - 00219606
TI - Strongly aligned molecules inside helium droplets in the near-adiabatic regime
VL - 147
ER -
TY - JOUR
AB - Recently it was shown that molecules rotating in superfluid helium can be described in terms of the angulon quasiparticles (Phys. Rev. Lett. 118, 095301 (2017)). Here we demonstrate that in the experimentally realized regime the angulon can be seen as a point charge on a 2-sphere interacting with a gauge field of a non-abelian magnetic monopole. Unlike in several other settings, the gauge fields of the angulon problem emerge in the real coordinate space, as opposed to the momentum space or some effective parameter space. Furthermore, we find a topological transition associated with making the monopole abelian, which takes place in the vicinity of the previously reported angulon instabilities. These results pave the way for studying topological phenomena in experiments on molecules trapped in superfluid helium nanodroplets, as well as on other realizations of orbital impurity problems.
AU - Yakaboylu, Enderalp
AU - Deuchert, Andreas
AU - Lemeshko, Mikhail
ID - 997
IS - 23
JF - APS Physics, Physical Review Letters
SN - 00319007
TI - Emergence of non-abelian magnetic monopoles in a quantum impurity problem
VL - 119
ER -
TY - CONF
AB - A major open problem on the road to artificial intelligence is the development of incrementally learning systems that learn about more and more concepts over time from a stream of data. In this work, we introduce a new training strategy, iCaRL, that allows learning in such a class-incremental way: only the training data for a small number of classes has to be present at the same time and new classes can be added progressively. iCaRL learns strong classifiers and a data representation simultaneously. This distinguishes it from earlier works that were fundamentally limited to fixed data representations and therefore incompatible with deep learning architectures. We show by experiments on CIFAR-100 and ImageNet ILSVRC 2012 data that iCaRL can learn many classes incrementally over a long period of time where other strategies quickly fail.
AU - Rebuffi, Sylvestre Alvise
AU - Kolesnikov, Alexander
AU - Sperl, Georg
AU - Lampert, Christoph
ID - 998
SN - 978-153860457-1
TI - iCaRL: Incremental classifier and representation learning
VL - 2017
ER -
TY - CONF
AB - In multi-task learning, a learner is given a collection of prediction tasks and needs to solve all of them. In contrast to previous work, which required that annotated training data must be available for all tasks, we consider a new setting, in which for some tasks, potentially most of them, only unlabeled training data is provided. Consequently, to solve all tasks, information must be transferred between tasks with labels and tasks without labels. Focusing on an instance-based transfer method we analyze two variants of this setting: when the set of labeled tasks is fixed, and when it can be actively selected by the learner. We state and prove a generalization bound that covers both scenarios and derive from it an algorithm for making the choice of labeled tasks (in the active case) and for transferring information between the tasks in a principled way. We also illustrate the effectiveness of the algorithm on synthetic and real data.
AU - Pentina, Anastasia
AU - Lampert, Christoph
ID - 999
SN - 9781510855144
TI - Multi-task learning with labeled and unlabeled tasks
VL - 70
ER -
TY - CHAP
AB - We show that very weak topological assumptions are enough to ensure the existence of a Helly-type theorem. More precisely, we show that for any non-negative integers b and d there exists an integer h(b, d) such that the following holds. If F is a finite family of subsets of Rd such that βi(∩G)≤b for any G⊊F and every 0 ≤ i ≤ [d/2]-1 then F has Helly number at most h(b, d). Here βi denotes the reduced Z2-Betti numbers (with singular homology). These topological conditions are sharp: not controlling any of these [d/2] first Betti numbers allow for families with unbounded Helly number. Our proofs combine homological non-embeddability results with a Ramsey-based approach to build, given an arbitrary simplicial complex K, some well-behaved chain map C*(K)→C*(Rd).
AU - Goaoc, Xavier
AU - Paták, Pavel
AU - Patakova, Zuzana
AU - Tancer, Martin
AU - Wagner, Uli
ED - Loebl, Martin
ED - Nešetřil, Jaroslav
ED - Thomas, Robin
ID - 424
SN - 978-331944479-6
T2 - A Journey through Discrete Mathematics: A Tribute to Jiri Matousek
TI - Bounding helly numbers via betti numbers
ER -
TY - CONF
AB - Parallel implementations of stochastic gradient descent (SGD) have received significant research attention, thanks to its excellent scalability properties. A fundamental barrier when parallelizing SGD is the high bandwidth cost of communicating gradient updates between nodes; consequently, several lossy compresion heuristics have been proposed, by which nodes only communicate quantized gradients. Although effective in practice, these heuristics do not always converge. In this paper, we propose Quantized SGD (QSGD), a family of compression schemes with convergence guarantees and good practical performance. QSGD allows the user to smoothly trade off communication bandwidth and convergence time: nodes can adjust the number of bits sent per iteration, at the cost of possibly higher variance. We show that this trade-off is inherent, in the sense that improving it past some threshold would violate information-theoretic lower bounds. QSGD guarantees convergence for convex and non-convex objectives, under asynchrony, and can be extended to stochastic variance-reduced techniques. When applied to training deep neural networks for image classification and automated speech recognition, QSGD leads to significant reductions in end-to-end training time. For instance, on 16GPUs, we can train the ResNet-152 network to full accuracy on ImageNet 1.8 × faster than the full-precision variant.
AU - Alistarh, Dan-Adrian
AU - Grubic, Demjan
AU - Li, Jerry
AU - Tomioka, Ryota
AU - Vojnović, Milan
ID - 431
SN - 10495258
TI - QSGD: Communication-efficient SGD via gradient quantization and encoding
VL - 2017
ER -
TY - CONF
AB - Recently there has been significant interest in training machine-learning models at low precision: by reducing precision, one can reduce computation and communication by one order of magnitude. We examine training at reduced precision, both from a theoretical and practical perspective, and ask: is it possible to train models at end-to-end low precision with provable guarantees? Can this lead to consistent order-of-magnitude speedups? We mainly focus on linear models, and the answer is yes for linear models. We develop a simple framework called ZipML based on one simple but novel strategy called double sampling. Our ZipML framework is able to execute training at low precision with no bias, guaranteeing convergence, whereas naive quanti- zation would introduce significant bias. We val- idate our framework across a range of applica- tions, and show that it enables an FPGA proto- type that is up to 6.5 × faster than an implemen- tation using full 32-bit precision. We further de- velop a variance-optimal stochastic quantization strategy and show that it can make a significant difference in a variety of settings. When applied to linear models together with double sampling, we save up to another 1.7 × in data movement compared with uniform quantization. When training deep networks with quantized models, we achieve higher accuracy than the state-of-the- art XNOR-Net.
AU - Zhang, Hantian
AU - Li, Jerry
AU - Kara, Kaan
AU - Alistarh, Dan-Adrian
AU - Liu, Ji
AU - Zhang, Ce
ID - 432
SN - 978-151085514-4
T2 - Proceedings of Machine Learning Research
TI - ZipML: Training linear models with end-to-end low precision, and a little bit of deep learning
VL - 70
ER -
TY - JOUR
AB - We introduce planar matchings on directed pseudo-line arrangements, which yield a planar set of pseudo-line segments such that only matching-partners are adjacent. By translating the planar matching problem into a corresponding stable roommates problem we show that such matchings always exist. Using our new framework, we establish, for the first time, a complete, rigorous definition of weighted straight skeletons, which are based on a so-called wavefront propagation process. We present a generalized and unified approach to treat structural changes in the wavefront that focuses on the restoration of weak planarity by finding planar matchings.
AU - Biedl, Therese
AU - Huber, Stefan
AU - Palfrader, Peter
ID - 481
IS - 3-4
JF - International Journal of Computational Geometry and Applications
TI - Planar matchings for weighted straight skeletons
VL - 26
ER -
TY - JOUR
AB - Two-player games on graphs provide the theoretical framework for many important problems such as reactive synthesis. While the traditional study of two-player zero-sum games has been extended to multi-player games with several notions of equilibria, they are decidable only for perfect-information games, whereas several applications require imperfect-information. In this paper we propose a new notion of equilibria, called doomsday equilibria, which is a strategy profile where all players satisfy their own objective, and if any coalition of players deviates and violates even one of the players' objective, then the objective of every player is violated. We present algorithms and complexity results for deciding the existence of doomsday equilibria for various classes of ω-regular objectives, both for imperfect-information games, and for perfect-information games. We provide optimal complexity bounds for imperfect-information games, and in most cases for perfect-information games.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Filiot, Emmanuel
AU - Raskin, Jean
ID - 681
JF - Information and Computation
SN - 08905401
TI - Doomsday equilibria for omega-regular games
VL - 254
ER -
TY - JOUR
AB - Auxin steers numerous physiological processes in plants, making the tight control of its endogenous levels and spatiotemporal distribution a necessity. This regulation is achieved by different mechanisms, including auxin biosynthesis, metabolic conversions, degradation, and transport. Here, we introduce cis-cinnamic acid (c-CA) as a novel and unique addition to a small group of endogenous molecules affecting in planta auxin concentrations. c-CA is the photo-isomerization product of the phenylpropanoid pathway intermediate trans-CA (t-CA). When grown on c-CA-containing medium, an evolutionary diverse set of plant species were shown to exhibit phenotypes characteristic for high auxin levels, including inhibition of primary root growth, induction of root hairs, and promotion of adventitious and lateral rooting. By molecular docking and receptor binding assays, we showed that c-CA itself is neither an auxin nor an anti-auxin, and auxin profiling data revealed that c-CA does not significantly interfere with auxin biosynthesis. Single cell-based auxin accumulation assays showed that c-CA, and not t-CA, is a potent inhibitor of auxin efflux. Auxin signaling reporters detected changes in spatiotemporal distribution of the auxin response along the root of c-CA-treated plants, and long-distance auxin transport assays showed no inhibition of rootward auxin transport. Overall, these results suggest that the phenotypes of c-CA-treated plants are the consequence of a local change in auxin accumulation, induced by the inhibition of auxin efflux. This work reveals a novel mechanism how plants may regulate auxin levels and adds a novel, naturally occurring molecule to the chemical toolbox for the studies of auxin homeostasis.
AU - Steenackers, Ward
AU - Klíma, Petr
AU - Quareshy, Mussa
AU - Cesarino, Igor
AU - Kumpf, Robert
AU - Corneillie, Sander
AU - Araújo, Pedro
AU - Viaene, Tom
AU - Goeminne, Geert
AU - Nowack, Moritz
AU - Ljung, Karin
AU - Friml, Jirí
AU - Blakeslee, Joshua
AU - Novák, Ondřej
AU - Zažímalová, Eva
AU - Napier, Richard
AU - Boerjan, Wout
AU - Vanholme, Bartel
ID - 1159
IS - 1
JF - Plant Physiology
SN - 0032-0889
TI - Cis-cinnamic acid is a novel natural auxin efflux inhibitor that promotes lateral root formation
VL - 173
ER -
TY - CHAP
AB - In the analysis of reactive systems a quantitative objective assigns a real value to every trace of the system. The value decision problem for a quantitative objective requires a trace whose value is at least a given threshold, and the exact value decision problem requires a trace whose value is exactly the threshold. We compare the computational complexity of the value and exact value decision problems for classical quantitative objectives, such as sum, discounted sum, energy, and mean-payoff for two standard models of reactive systems, namely, graphs and graph games.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Henzinger, Thomas A
ED - Aceto, Luca
ED - Bacci, Giorgio
ED - Ingólfsdóttir, Anna
ED - Legay, Axel
ED - Mardare, Radu
ID - 625
SN - 0302-9743
T2 - Models, Algorithms, Logics and Tools
TI - The cost of exactness in quantitative reachability
VL - 10460
ER -
TY - BOOK
AB - This book is a concise and self-contained introduction of recent techniques to prove local spectral universality for large random matrices. Random matrix theory is a fast expanding research area, and this book mainly focuses on the methods that the authors participated in developing over the past few years. Many other interesting topics are not included, and neither are several new developments within the framework of these methods. The authors have chosen instead to present key concepts that they believe are the core of these methods and should be relevant for future applications. They keep technicalities to a minimum to make the book accessible to graduate students. With this in mind, they include in this book the basic notions and tools for high-dimensional analysis, such as large deviation, entropy, Dirichlet form, and the logarithmic Sobolev inequality.
AU - Erdös, László
AU - Yau, Horng
ID - 567
SN - 9-781-4704-3648-3
TI - A Dynamical Approach to Random Matrix Theory
VL - 28
ER -
TY - CHAP
AB - We give a short overview on a recently developed notion of Ricci curvature for discrete spaces. This notion relies on geodesic convexity properties of the relative entropy along geodesics in the space of probability densities, for a metric which is similar to (but different from) the 2-Wasserstein metric. The theory can be considered as a discrete counterpart to the theory of Ricci curvature for geodesic measure spaces developed by Lott–Sturm–Villani.
AU - Maas, Jan
ED - Najman, Laurent
ED - Romon, Pascal
ID - 649
SN - 978-3-319-58001-2
T2 - Modern Approaches to Discrete Curvature
TI - Entropic Ricci curvature for discrete spaces
VL - 2184
ER -
TY - GEN
AB - This book constitutes the refereed proceedings of the 9th InternationalWorkshop on Numerical Software Verification, NSV 2016, held in Toronto, ON, Canada in July 2011 - colocated with CAV 2016, the 28th International Conference on Computer Aided Verification.
The NSV workshop is dedicated to the development of logical and mathematical techniques for the reasoning about programmability and reliability.
ED - Bogomolov, Sergiy
ED - Martel, Matthieu
ED - Prabhakar, Pavithra
ID - 638
SN - 0302-9743
TI - Numerical Software Verification
VL - 10152
ER -
TY - JOUR
AB - We consider N×N Hermitian random matrices H consisting of blocks of size M≥N6/7. The matrix elements are i.i.d. within the blocks, close to a Gaussian in the four moment matching sense, but their distribution varies from block to block to form a block-band structure, with an essential band width M. We show that the entries of the Green’s function G(z)=(H−z)−1 satisfy the local semicircle law with spectral parameter z=E+iη down to the real axis for any η≫N−1, using a combination of the supersymmetry method inspired by Shcherbina (J Stat Phys 155(3): 466–499, 2014) and the Green’s function comparison strategy. Previous estimates were valid only for η≫M−1. The new estimate also implies that the eigenvectors in the middle of the spectrum are fully delocalized.
AU - Bao, Zhigang
AU - Erdös, László
ID - 1528
IS - 3-4
JF - Probability Theory and Related Fields
SN - 01788051
TI - Delocalization for a class of random block band matrices
VL - 167
ER -
TY - THES
AB - Restriction-modification (RM) represents the simplest and possibly the most widespread mechanism of self/non-self discrimination in nature. In order to provide bacteria with immunity against bacteriophages and other parasitic genetic elements, RM systems rely on a balance between two enzymes: the restriction enzyme, which cleaves non-self DNA at specific restriction sites, and the modification enzyme, which tags the host’s DNA as self and thus protects it from cleavage. In this thesis, I use population and single-cell level experiments in combination with mathematical modeling to study different aspects of the interplay between RM systems, bacteria and bacteriophages. First, I analyze how mutations in phage restriction sites affect the probability of phage escape – an inherently stochastic process, during which phages accidently get modified instead of restricted. Next, I use single-cell experiments to show that RM systems can, with a low probability, attack the genome of their bacterial host and that this primitive form of autoimmunity leads to a tradeoff between the evolutionary cost and benefit of RM systems. Finally, I investigate the nature of interactions between bacteria, RM systems and temperate bacteriophages to find that, as a consequence of phage escape and its impact on population dynamics, RM systems can promote acquisition of symbiotic bacteriophages, rather than limit it. The results presented here uncover new fundamental biological properties of RM systems and highlight their importance in the ecology and evolution of bacteria, bacteriophages and their interactions.
AU - Pleska, Maros
ID - 202
TI - Biology of restriction-modification systems at the single-cell and population level
ER -
TY - JOUR
AB - From microwave ovens to satellite television to the GPS and data services on our mobile phones, microwave technology is everywhere today. But one technology that has so far failed to prove its worth in this wavelength regime is quantum communication that uses the states of single photons as information carriers. This is because single microwave photons, as opposed to classical microwave signals, are extremely vulnerable to noise from thermal excitations in the channels through which they travel. Two new independent studies, one by Ze-Liang Xiang at Technische Universität Wien (Vienna), Austria, and colleagues [1] and another by Benoît Vermersch at the University of Innsbruck, also in Austria, and colleagues [2] now describe a theoretical protocol for microwave quantum communication that is resilient to thermal and other types of noise. Their approach could become a powerful technique to establish fast links between superconducting data processors in a future all-microwave quantum network.
AU - Fink, Johannes M
ID - 1013
IS - 32
JF - Physics
TI - Viewpoint: Microwave quantum states beat the heat
VL - 10
ER -
TY - JOUR
AB - The extent of heterogeneity among driver gene mutations present in naturally occurring metastases - that is, treatment-naive metastatic disease - is largely unknown. To address this issue, we carried out 60× whole-genome sequencing of 26 metastases from four patients with pancreatic cancer. We found that identical mutations in known driver genes were present in every metastatic lesion for each patient studied. Passenger gene mutations, which do not have known or predicted functional consequences, accounted for all intratumoral heterogeneity. Even with respect to these passenger mutations, our analysis suggests that the genetic similarity among the founding cells of metastases was higher than that expected for any two cells randomly taken from a normal tissue. The uniformity of known driver gene mutations among metastases in the same patient has critical and encouraging implications for the success of future targeted therapies in advanced-stage disease.
AU - Makohon Moore, Alvin
AU - Zhang, Ming
AU - Reiter, Johannes
AU - Božić, Ivana
AU - Allen, Benjamin
AU - Kundu, Deepanjan
AU - Chatterjee, Krishnendu
AU - Wong, Fay
AU - Jiao, Yuchen
AU - Kohutek, Zachary
AU - Hong, Jungeui
AU - Attiyeh, Marc
AU - Javier, Breanna
AU - Wood, Laura
AU - Hruban, Ralph
AU - Nowak, Martin
AU - Papadopoulos, Nickolas
AU - Kinzler, Kenneth
AU - Vogelstein, Bert
AU - Iacobuzio Donahue, Christine
ID - 653
IS - 3
JF - Nature Genetics
SN - 10614036
TI - Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer
VL - 49
ER -
TY - JOUR
AB - Since 2006, reprogrammed cells have increasingly been used as a biomedical research technique in addition to neuro-psychiatric methods. These rapidly evolving techniques allow for the generation of neuronal sub-populations, and have sparked interest not only in monogenetic neuro-psychiatric diseases, but also in poly-genetic and poly-aetiological disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). This review provides a summary of 19 publications on reprogrammed adult somatic cells derived from patients with SCZ, and five publications using this technique in patients with BPD. As both disorders are complex and heterogeneous, there is a plurality of hypotheses to be tested in vitro. In SCZ, data on alterations of dopaminergic transmission in vitro are sparse, despite the great explanatory power of the so-called DA hypothesis of SCZ. Some findings correspond to perturbations of cell energy metabolism, and observations in reprogrammed cells suggest neuro-developmental alterations. Some studies also report on the efficacy of medicinal compounds to revert alterations observed in cellular models. However, due to the paucity of replication studies, no comprehensive conclusions can be drawn from studies using reprogrammed cells at the present time. In the future, findings from cell culture methods need to be integrated with clinical, epidemiological, pharmacological and imaging data in order to generate a more comprehensive picture of SCZ and BPD.
AU - Sauerzopf, Ulrich
AU - Sacco, Roberto
AU - Novarino, Gaia
AU - Niello, Marco
AU - Weidenauer, Ana
AU - Praschak Rieder, Nicole
AU - Sitte, Harald
AU - Willeit, Matthaeus
ID - 1228
IS - 1
JF - European Journal of Neuroscience
TI - Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence
VL - 45
ER -
TY - THES
AB - Cell-cell contact formation constitutes the first step in the emergence of multicellularity in evolution, thereby allowing the differentiation of specialized cell types. In metazoan development, cell-cell contact formation is thought to influence cell fate specification, and cell fate specification has been implicated in cell-cell contact formation. However, remarkably little is yet known about whether and how the interaction and feedback between cell-cell contact formation and cell fate specification affect development. Here we identify a positive feedback loop between cell-cell contact duration, morphogen signaling and mesendoderm cell fate specification during zebrafish gastrulation. We show that long lasting cell-cell contacts enhance the competence of prechordal plate (ppl) progenitor cells to respond to Nodal signaling, required for proper ppl cell fate specification. We further show that Nodal signalling romotes ppl cell-cell contact duration, thereby generating an effective positive feedback loop between ppl cell-cell contact duration and cell fate specification. Finally, by using a combination of theoretical modeling and experimentation, we show that this feedback loop determines whether anterior axial mesendoderm cells become ppl progenitors or, instead, turn into endoderm progenitors. Our findings reveal that the gene regulatory networks leading to cell fate diversification within the developing embryo are controlled by the interdependent activities of cell-cell signaling and contact formation.
AU - Barone, Vanessa
ID - 961
TI - Cell adhesion and cell fate: An effective feedback loop during zebrafish gastrulation
ER -
TY - JOUR
AB - The optogenetic revolution enabled spatially-precise and temporally-precise control over protein function, signaling pathway activation, and animal behavior with tremendous success in the dissection of signaling networks and neural circuits. Very recently, optogenetic methods have been paired with optical reporters in novel drug screening platforms. In these all-optical platforms, light remotely activated ion channels and kinases thereby obviating the use of electrophysiology or reagents. Consequences were remarkable operational simplicity, throughput, and cost-effectiveness that culminated in the identification of new drug candidates. These blueprints for all-optical assays also revealed potential pitfalls and inspire all-optical variants of other screens, such as those that aim at better understanding dynamic drug action or orphan protein function.
AU - Agus, Viviana
AU - Janovjak, Harald L
ID - 1026
JF - Current Opinion in Biotechnology
SN - 09581669
TI - Optogenetic methods in drug screening: Technologies and applications
VL - 48
ER -
TY - JOUR
AB - Phat is an open-source C. ++ library for the computation of persistent homology by matrix reduction, targeted towards developers of software for topological data analysis. We aim for a simple generic design that decouples algorithms from data structures without sacrificing efficiency or user-friendliness. We provide numerous different reduction strategies as well as data types to store and manipulate the boundary matrix. We compare the different combinations through extensive experimental evaluation and identify optimization techniques that work well in practical situations. We also compare our software with various other publicly available libraries for persistent homology.
AU - Bauer, Ulrich
AU - Kerber, Michael
AU - Reininghaus, Jan
AU - Wagner, Hubert
ID - 1433
JF - Journal of Symbolic Computation
SN - 07477171
TI - Phat - Persistent homology algorithms toolbox
VL - 78
ER -
TY - JOUR
AB - Heavy holes confined in quantum dots are predicted to be promising candidates for the realization of spin qubits with long coherence times. Here we focus on such heavy-hole states confined in germanium hut wires. By tuning the growth density of the latter we can realize a T-like structure between two neighboring wires. Such a structure allows the realization of a charge sensor, which is electrostatically and tunnel coupled to a quantum dot, with charge-transfer signals as high as 0.3 e. By integrating the T-like structure into a radiofrequency reflectometry setup, single-shot measurements allowing the extraction of hole tunneling times are performed. The extracted tunneling times of less than 10 μs are attributed to the small effective mass of Ge heavy-hole states and pave the way toward projective spin readout measurements.
AU - Vukusic, Lada
AU - Kukucka, Josip
AU - Watzinger, Hannes
AU - Katsaros, Georgios
ID - 840
IS - 9
JF - Nano Letters
SN - 15306984
TI - Fast hole tunneling times in germanium hut wires probed by single-shot reflectometry
VL - 17
ER -
TY - CONF
AB - Graph games provide the foundation for modeling and synthesis of reactive processes. Such games are played over graphs where the vertices are controlled by two adversarial players. We consider graph games where the objective of the first player is the conjunction of a qualitative objective (specified as a parity condition) and a quantitative objective (specified as a meanpayoff condition). There are two variants of the problem, namely, the threshold problem where the quantitative goal is to ensure that the mean-payoff value is above a threshold, and the value problem where the quantitative goal is to ensure the optimal mean-payoff value; in both cases ensuring the qualitative parity objective. The previous best-known algorithms for game graphs with n vertices, m edges, parity objectives with d priorities, and maximal absolute reward value W for mean-payoff objectives, are as follows: O(nd+1 . m . w) for the threshold problem, and O(nd+2 · m · W) for the value problem. Our main contributions are faster algorithms, and the running times of our algorithms are as follows: O(nd-1 · m ·W) for the threshold problem, and O(nd · m · W · log(n · W)) for the value problem. For mean-payoff parity objectives with two priorities, our algorithms match the best-known bounds of the algorithms for mean-payoff games (without conjunction with parity objectives). Our results are relevant in synthesis of reactive systems with both functional requirement (given as a qualitative objective) and performance requirement (given as a quantitative objective).
AU - Chatterjee, Krishnendu
AU - Henzinger, Monika H
AU - Svozil, Alexander
ID - 552
SN - 978-395977046-0
T2 - Leibniz International Proceedings in Informatics
TI - Faster algorithms for mean-payoff parity games
VL - 83
ER -
TY - CONF
AB - Graph games with omega-regular winning conditions provide a mathematical framework to analyze a wide range of problems in the analysis of reactive systems and programs (such as the synthesis of reactive systems, program repair, and the verification of branching time properties). Parity conditions are canonical forms to specify omega-regular winning conditions. Graph games with parity conditions are equivalent to mu-calculus model checking, and thus a very important algorithmic problem. Symbolic algorithms are of great significance because they provide scalable algorithms for the analysis of large finite-state systems, as well as algorithms for the analysis of infinite-state systems with finite quotient. A set-based symbolic algorithm uses the basic set operations and the one-step predecessor operators. We consider graph games with n vertices and parity conditions with c priorities (equivalently, a mu-calculus formula with c alternations of least and greatest fixed points). While many explicit algorithms exist for graph games with parity conditions, for set-based symbolic algorithms there are only two algorithms (notice that we use space to refer to the number of sets stored by a symbolic algorithm): (a) the basic algorithm that requires O(n^c) symbolic operations and linear space; and (b) an improved algorithm that requires O(n^{c/2+1}) symbolic operations but also O(n^{c/2+1}) space (i.e., exponential space). In this work we present two set-based symbolic algorithms for parity games: (a) our first algorithm requires O(n^{c/2+1}) symbolic operations and only requires linear space; and (b) developing on our first algorithm, we present an algorithm that requires O(n^{c/3+1}) symbolic operations and only linear space. We also present the first linear space set-based symbolic algorithm for parity games that requires at most a sub-exponential number of symbolic operations.
AU - Chatterjee, Krishnendu
AU - Dvorák, Wolfgang
AU - Henzinger, Monika H
AU - Loitzenbauer, Veronika
ID - 6519
TI - Improved set-based symbolic algorithms for parity games
VL - 82
ER -
TY - JOUR
AB - The computation of the winning set for parity objectives and for Streett objectives in graphs as well as in game graphs are central problems in computer-aided verification, with application to the verification of closed systems with strong fairness conditions, the verification of open systems, checking interface compatibility, well-formedness of specifications, and the synthesis of reactive systems. We show how to compute the winning set on n vertices for (1) parity-3 (aka one-pair Streett) objectives in game graphs in time O(n5/2) and for (2) k-pair Streett objectives in graphs in time O(n2+nklogn). For both problems this gives faster algorithms for dense graphs and represents the first improvement in asymptotic running time in 15 years.
AU - Chatterjee, Krishnendu
AU - Henzinger, Monika H
AU - Loitzenbauer, Veronika
ID - 464
IS - 3
JF - Logical Methods in Computer Science
SN - 18605974
TI - Improved algorithms for parity and Streett objectives
VL - 13
ER -
TY - GEN
AB - Branching morphogenesis of the epithelial ureteric bud forms the renal collecting duct system and is critical for normal nephron number, while low nephron number is implicated in hypertension and renal disease. Ureteric bud growth and branching requires GDNF signaling from the surrounding mesenchyme to cells at the ureteric bud tips, via the Ret receptor tyrosine kinase and coreceptor Gfrα1; Ret signaling up-regulates transcription factors Etv4 and Etv5, which are also critical for branching. Despite extensive knowledge of the genetic control of these events, it is not understood, at the cellular level, how renal branching morphogenesis is achieved or how Ret signaling influences epithelial cell behaviors to promote this process. Analysis of chimeric embryos previously suggested a role for Ret signaling in promoting cell rearrangements in the nephric duct, but this method was unsuited to study individual cell behaviors during ureteric bud branching. Here, we use Mosaic Analysis with Double Markers (MADM), combined with organ culture and time-lapse imaging, to trace the movements and divisions of individual ureteric bud tip cells. We first examine wild-type clones and then Ret or Etv4 mutant/wild-type clones in which the mutant and wild-type sister cells are differentially and heritably marked by green and red fluorescent proteins. We find that, in normal kidneys, most individual tip cells behave as self-renewing progenitors, some of whose progeny remain at the tips while others populate the growing UB trunks. In Ret or Etv4 MADM clones, the wild-type cells generated at a UB tip are much more likely to remain at, or move to, the new tips during branching and elongation, while their Ret−/− or Etv4−/− sister cells tend to lag behind and contribute only to the trunks. By tracking successive mitoses in a cell lineage, we find that Ret signaling has little effect on proliferation, in contrast to its effects on cell movement. Our results show that Ret/Etv4 signaling promotes directed cell movements in the ureteric bud tips, and suggest a model in which these cell movements mediate branching morphogenesis.
AU - Riccio, Paul
AU - Cebrián, Christina
AU - Zong, Hui
AU - Hippenmeyer, Simon
AU - Costantini, Frank
ID - 9707
TI - Data from: Ret and Etv4 promote directed movements of progenitor cells during renal branching morphogenesis
ER -
TY - GEN
AB - Across the nervous system, certain population spiking patterns are observed far more frequently than others. A hypothesis about this structure is that these collective activity patterns function as population codewords–collective modes–carrying information distinct from that of any single cell. We investigate this phenomenon in recordings of ∼150 retinal ganglion cells, the retina’s output. We develop a novel statistical model that decomposes the population response into modes; it predicts the distribution of spiking activity in the ganglion cell population with high accuracy. We found that the modes represent localized features of the visual stimulus that are distinct from the features represented by single neurons. Modes form clusters of activity states that are readily discriminated from one another. When we repeated the same visual stimulus, we found that the same mode was robustly elicited. These results suggest that retinal ganglion cells’ collective signaling is endowed with a form of error-correcting code–a principle that may hold in brain areas beyond retina.
AU - Prentice, Jason
AU - Marre, Olivier
AU - Ioffe, Mark
AU - Loback, Adrianna
AU - Tkačik, Gašper
AU - Berry, Michael
ID - 9709
TI - Data from: Error-robust modes of the retinal population code
ER -
TY - JOUR
AB - Much of quantitative genetics is based on the ‘infinitesimal model’, under which selection has a negligible effect on the genetic variance. This is typically justified by assuming a very large number of loci with additive effects. However, it applies even when genes interact, provided that the number of loci is large enough that selection on each of them is weak relative to random drift. In the long term, directional selection will change allele frequencies, but even then, the effects of epistasis on the ultimate change in trait mean due to selection may be modest. Stabilising selection can maintain many traits close to their optima, even when the underlying alleles are weakly selected. However, the number of traits that can be optimised is apparently limited to ~4Ne by the ‘drift load’, and this is hard to reconcile with the apparent complexity of many organisms. Just as for the mutation load, this limit can be evaded by a particular form of negative epistasis. A more robust limit is set by the variance in reproductive success. This suggests that selection accumulates information most efficiently in the infinitesimal regime, when selection on individual alleles is weak, and comparable with random drift. A review of evidence on selection strength suggests that although most variance in fitness may be because of alleles with large Nes, substantial amounts of adaptation may be because of alleles in the infinitesimal regime, in which epistasis has modest effects.
AU - Barton, Nicholas H
ID - 1199
JF - Heredity
TI - How does epistasis influence the response to selection?
VL - 118
ER -
TY - GEN
AB - Mathematica notebooks used to generate figures.
AU - Etheridge, Alison
AU - Barton, Nicholas H
ID - 9842
TI - Data for: Establishment in a new habitat by polygenic adaptation
ER -
TY - JOUR
AB - Infections with potentially lethal pathogens may negatively affect an individual’s lifespan and decrease its reproductive value. The terminal investment hypothesis predicts that individuals faced with a reduced survival should invest more into reproduction instead of maintenance and growth. Several studies suggest that individuals are indeed able to estimate their body condition and to increase their reproductive effort with approaching death, while other studies gave ambiguous results. We investigate whether queens of a perennial social insect (ant) are able to boost their reproduction following infection with an obligate killing pathogen. Social insect queens are special with regard to reproduction and aging, as they outlive conspecific non-reproductive workers. Moreover, in the ant Cardiocondyla obscurior, fecundity increases with queen age. However, it remained unclear whether this reflects negative reproductive senescence or terminal investment in response to approaching death. Here, we test whether queens of C. obscurior react to infection with the entomopathogenic fungus Metarhizium brunneum by an increased egg-laying rate. We show that a fungal infection triggers a reinforced investment in reproduction in queens. This adjustment of the reproductive rate by ant queens is consistent with predictions of the terminal investment hypothesis and is reported for the first time in a social insect.
AU - Giehr, Julia
AU - Grasse, Anna V
AU - Cremer, Sylvia
AU - Heinze, Jürgen
AU - Schrempf, Alexandra
ID - 914
IS - 7
JF - Royal Society Open Science
SN - 20545703
TI - Ant queens increase their reproductive efforts after pathogen infection
VL - 4
ER -
TY - JOUR
AB - Restriction–modification systems are widespread genetic elements that protect bacteria from bacteriophage infections by recognizing and cleaving heterologous DNA at short, well-defined sequences called restriction sites. Bioinformatic evidence shows that restriction sites are significantly underrepresented in bacteriophage genomes, presumably because bacteriophages with fewer restriction sites are more likely to escape cleavage by restriction–modification systems. However, how mutations in restriction sites affect the likelihood of bacteriophage escape is unknown. Using the bacteriophage l and the restriction–modification system EcoRI, we show that while mutation effects at different restriction sites are unequal, they are independent. As a result, the probability of bacteriophage escape increases with each mutated restriction site. Our results experimentally support the role of restriction site avoidance as a response to selection imposed by restriction–modification systems and offer an insight into the events underlying the process of bacteriophage escape.
AU - Pleska, Maros
AU - Guet, Calin C
ID - 561
IS - 12
JF - Biology Letters
SN - 1744-9561
TI - Effects of mutations in phage restriction sites during escape from restriction–modification
VL - 13
ER -
TY - GEN
AB - Lists of all differentially expressed genes in the different priming-challenge treatments (compared to the fully naïve control; xlsx file). Relevant columns include the following: sample_1 and sample_2 – treatment groups being compared; Normalised FPKM sample_1 and sample_2 – FPKM of samples being compared; log2(fold_change) – log2(FPKM sample 2/FPKM sample 1), i.e. negative means sample 1 upregulated compared with sample 2, positive means sample 2 upregulated compared with sample 1; cuffdiff test_statistic – test statistic of differential expression test; p_value – p-value of differential expression test; q_value (FDR correction) – adjusted P-value of differential expression test. (XLSX 598 kb)
AU - Greenwood, Jenny
AU - Milutinovic, Barbara
AU - Peuß, Robert
AU - Behrens, Sarah
AU - Essar, Daniela
AU - Rosenstiel, Philip
AU - Schulenburg, Hinrich
AU - Kurtz, Joachim
ID - 9859
TI - Additional file 1: Table S1. of Oral immune priming with Bacillus thuringiensis induces a shift in the gene expression of Tribolium castaneum larvae
ER -
TY - GEN
AB - information on culture conditions, phage mutagenesis, verification and lysate preparation; Raw data
AU - Pleska, Maros
AU - Guet, Calin C
ID - 9847
TI - Supplementary materials and methods; Full data set from effects of mutations in phage restriction sites during escape from restriction–modification
ER -
TY - GEN
AB - Egg laying rates and infection loads of C. obscurior queens
AU - Giehr, Julia
AU - Grasse, Anna V
AU - Cremer, Sylvia
AU - Heinze, Jürgen
AU - Schrempf, Alexandra
ID - 9853
TI - Raw data from ant queens increase their reproductive efforts after pathogen infection
ER -